Prospective Analysis Research Articles

The accuracy of anal self- and companion exams among sexual minority men and transgender women: a prospective analysis

Squamous cell carcinoma of the anus (SCCA) annual incidence among sexual minority men with and without HIV is 85/100,000 and 19/100,000 persons, respectively, which is significantly higher than the overall incidence (2/100,000). Incidence may also be higher in transgender women. Since SCCA tumours average ≥30mm at diagnosis, we assessed the accuracy of individuals to self-detect smaller anal abnormalities. Using convenience sampling, the study enrolled sexual minority men and transgender women, aged 25-81 years, in Chicago, Illinois and Houston, Texas, USA, during 2020-2022. Individuals were taught the anal self-examination and anal companion examination (ASE/ACE). Then, a clinician performed a digital anal rectal examination (DARE) before participants conducted the ASE or ACE. The sensitivity, specificity and concordance of the ASE/ACE to detect an abnormality were measured along with factors associated with ASE/ACE and DARE concordance. Among 714 enrolled individuals, the median age was 40 years (interquartile range, 32-54), 36.8% (259/703) were living with HIV, and 47.0% (334/710), 23.4% (166/710), and 23.0% (163/710) were non-Hispanic white, non-Hispanic Black, and Hispanic, respectively. A total of 94.1% (671/713) identified as cisgendered men, and 5.9% (42/713) as gender minorities. A total of 658 participants completed an ASE and 28 couples (56 partners) completed an ACE. Clinicians detected abnormalities in 34.3% (245/714) of individuals. The abnormalities were a median of 3mm in diameter. Sensitivity and specificity of the ASE/ACE was 59.6% (95% CI 53.5-65.7%) and 80.2% (95% CI 76.6-83.8%), respectively. Overall concordance was 0.73 (95% CI 0.70-0.76) between ASE/ACE and DARE and increased with increasing anal canal lesion size (p=0.02). Concordance was lower when participants were older and received ASE/ACE training from a lay person rather than a clinician. Sexual minority men/transgender women may self-detect SCCA when malignant lesions are much smaller than the current mean dimension at presentation of ≥30mm. National Cancer Institute.

Study on the Manufacturability of XDFOI Package with Organic RDLs (XDFOI-O)

The concept of chiplet has been proposed in the post Moore era, while how to achieve the layout of multiple chips of different processes and sizes in the manufacturing process is a coming problem that needs to be considered. Different layouts may significantly affect the manufacturability during the packaging process. Prospective finite element analysis (FEA) can evaluate various layouts by optimizing the layout and increasing the placement of dummy chips as stiffeners, thereby selecting the best layout and combination method. In addition, the characteristic of chiplet packaging is that multiple chips may come from different sources, such as different foundries, processes, sizes, or even thicknesses. This really poses challenges to the subsequent flip chip and wafer thinning process for leveling the total package. It is necessary to confirm the evaluation of the impact of chips with different thicknesses and underfill coverage in the process, so as to ensure the consistency in processing and improve the yield of packages.

Aggressive lipid-lowering treatment in Managed Care after Acute Myocardial Infarction (MC-AMI) patients - results better but still not sufficient: A single center prospective analysis.

Aggressive lipid-lowering treatment in Managed Care after Acute Myocardial Infarction (MC-AMI) patients - results better but still not sufficient: A single center prospective analysis.

Evaluation of unenhanced three-dimensional endoanal ultrasound scan in preoperative assessment of perianal sepsis

Background: Perianal sepsis which includes perianal fistula and abscess is a common clinical condition that requires thorough preoperative evaluation to decrease the recurrence rate and to plan relevant surgery according to the anatomy of the fistula. MRI and 3D EAUS are two important preoperative investigations that delineate the anatomy of simple and complex fistula tracts. Due to lower cost and easier use 3D EAUS is a safe and reliable first-line investigation in evaluating perianal abscess. Methods: This is a retrospective and prospective analysis of patients with perianal sepsis who underwent pre-operative unenhanced 3D-EAUS in the departments of Colorectal surgery, Gastrointestinal surgery, and General surgery in our hospital. A B-K medical 2052 transducer was used for the study and the surgical assessment was done by multiple surgeons from multiple departments. Results: A total of 255 patients were assessed. The accuracy for primary fistula tracts and internal opening was 83.53% and 88.62% respectively. The kappa coefficient of correlation was k=0.70 (substantial agreement) for the fistula tract and k=0.81 (near perfect agreement) for the internal opening. The sensitivity, and specificity of primary tracts and internal openings were calculated. Transphincteric fistulas were 57% in our study. Conclusions: Unenhanced 3D EAUS is a reliable first-line investigation in preoperative evaluation of perianal fistula and abscess. Transphincteric fistula is the most common type of fistula. There is a high chance of correlation for the primary tract if a non-colorectal specialist performs the fistula surgery after 3D-EAUS without blinding.

Loneliness, belonging and psychosomatic complaints across late adolescence and young adulthood: a Swedish cohort study

BackgroundLoneliness and belonging refer to social connectedness and are associated with young people’s health; however, the relationship between these constructs and their impact on health is still being discussed. A dual continuum model of belonging and loneliness has been suggested, consisting of four groups depending on the state of loneliness and belonging: socially fulfilled (low loneliness, high belonging), socially indifferent (low loneliness, low belonging), socially searching (high loneliness, high belonging), and socially distressed (high loneliness, low belonging). The aim of this study is to examine loneliness and belonging in a Swedish sample of 17–18-years-olds who were followed over 3 years, and the associations that these aspects share with young people’s psychosomatic complaints during these ages.MethodsSwedish cohort data collected among late adolescents (age 17–18 in 2019) who were followed up in young adulthood (age 20–21 in 2022) (n = 2684) was used to examine the associations between loneliness, belonging, and psychosomatic complaints. Loneliness and belonging were measured by single items and the cross-combinations of these. Three psychosomatic complaints were assessed: stomach ache, headache, and difficulties falling asleep, and a summary index was calculated.ResultsLinear regression analyses showed that loneliness was positively and belonging was negatively cross-sectionally associated with psychosomatic complaints. The socially fulfilled group reported fewer psychosomatic complaints compared to all other groups, while the socially distressed group reported the highest level of psychosomatic complaints. Additional adjustment for sociodemographic characteristics barely affected the estimates. The prospective analysis supported these patterns; however, after adjustment for earlier psychosomatic complaints, the only statistically significant difference in subsequent psychosomatic complaints was found between the socially fulfilled and the socially distressed groups.ConclusionsLoneliness and belonging (separately and the cross-combinations of these) were cross-sectionally associated with psychosomatic complaints in late adolescence and in young adulthood. Prospectively, only the most vulnerable group in the dual continuum model, the socially distressed group, experienced more psychosomatic complaints than the socially fulfilled group, indicating a temporal relationship. Knowledge about the more nuanced links may be useful for developing specific public health recommendations and interventions for youth, targeting the most vulnerable groups.

Evaluating referrals of flashing lights and floaters coming into secondary care from primary care

ABSTRACT Clinical Relevance Optometrists should look to take every opportunity to expand their knowledge, understanding and skills pertaining to vitreoretinal conditions. Background Despite the existence of acute eye care schemes and the up-skilling of optometrists, many units are still noticing large numbers of poor-quality referrals with high false positive rates. The authors pondered whether these schemes are effective. Methods At two different time points, a prospective analysis of patients took place, of all the flashing lights and floaters referrals coming into secondary care at the Royal Glamorgan Hospital, Wales, UK. The following data was captured: the exact source of the primary care referral, the diagnosis being queried, the secondary care diagnoses made and the secondary care management decisions. The accuracy of retinal break and Shafer’s sign detection were also directly compared between primary care and secondary care using Cohen’s Kappa Coefficient. Results For the 2018 period, n = 51 patients were included. For the 2022–23 period n = 100 patients were included. The majority of referrals during both periods were from optometrists (>80%) via the WECS pathway. The most common diagnoses being queried were retinal breaks (~50%), followed by retinal detachments (~20%). Interestingly up to 20% of patients seen in secondary care were diagnosed as normal examinations and ~ 20%. Over 1/3 of patients were discharged after their first visit to the EEC. Statistically significant differences were found between the accuracy of retinal tear and Shafer’s identification between the primary and secondary care settings. Conclusion A high number of false positive referrals are coming into secondary care from the WECS pathway and clear training and education needs have been identified.

Prognostic factors and survival of breast cancer in patients over 40 years of age

Aims: Breast cancer is the cancer with the highest incidence and mortality in women. There are differences in prognosis and survival between women over and under the age of 40. In this article, we aimed to examine breast cancer prognostic factors and survival results in people over the age of 40. Methods: 1187 patients aged 40 and over who underwent surgery at the Ondokuz Mayıs University Department of General Surgery between August 2005 and April 2019 and whose data were accessible were retrospectively examined. Data were obtained from the hospital automation system, the Ministry of Health’s online database, hospital archives, patients, and/or their relatives. They were classified separately in terms of type of surgery, axillary metastasis status (according to radiological status if axilla surgery is not performed), type of axilla surgery performed, pathological tumor size, number of pathological lymph nodes, pathological stage, lymphovascular and perineural invasion status, hormone receptor positivity, C-erb B2 and Ki-67 status, neoadjuvant treatment status, and molecular subgroup. Variables were analyzed individually for recurrence, mortality, and survival. Results found to be significant were subjected to multivariate analysis testing. Statistical significance was accepted as p<0.05. Results: As a result of multivariate analysis performed by excluding data that disrupted homogeneous distribution, perineural invasion, lymphovascular invasion, grade, and progesterone receptor status were determined to be independent prognostic factors in terms of recurrence. Lymphovascular invasion and progesterone receptor status were found to be independent prognostic factors for mortality. Conclusion: A lot of studies have been conducted, and criteria have been determined for breast cancer prognosis and survival. In our results, lymphovascular invasion and progesterone receptor status were found to be independent prognostic markers for both recurrence and mortality. More reliable results can be obtained with prospective study analyses.

Combining full-length gene assay and SpliceAI to interpret the splicing impact of all possible SPINK1 coding variants

BackgroundSingle-nucleotide variants (SNVs) within gene coding sequences can significantly impact pre-mRNA splicing, bearing profound implications for pathogenic mechanisms and precision medicine. In this study, we aim to harness the well-established full-length gene splicing assay (FLGSA) in conjunction with SpliceAI to prospectively interpret the splicing effects of all potential coding SNVs within the four-exon SPINK1 gene, a gene associated with chronic pancreatitis.ResultsOur study began with a retrospective analysis of 27 SPINK1 coding SNVs previously assessed using FLGSA, proceeded with a prospective analysis of 35 new FLGSA-tested SPINK1 coding SNVs, followed by data extrapolation, and ended with further validation. In total, we analyzed 67 SPINK1 coding SNVs, which account for 9.3% of the 720 possible coding SNVs. Among these 67 FLGSA-analyzed SNVs, 12 were found to impact splicing. Through detailed comparison of FLGSA results and SpliceAI predictions, we inferred that the remaining 653 untested coding SNVs in the SPINK1 gene are unlikely to significantly affect splicing. Of the 12 splice-altering events, nine produced both normally spliced and aberrantly spliced transcripts, while the remaining three only generated aberrantly spliced transcripts. These splice-impacting SNVs were found solely in exons 1 and 2, notably at the first and/or last coding nucleotides of these exons. Among the 12 splice-altering events, 11 were missense variants (2.17% of 506 potential missense variants), and one was synonymous (0.61% of 164 potential synonymous variants). Notably, adjusting the SpliceAI cut-off to 0.30 instead of the conventional 0.20 would improve specificity without reducing sensitivity.ConclusionsBy integrating FLGSA with SpliceAI, we have determined that less than 2% (1.67%) of all possible coding SNVs in SPINK1 significantly influence splicing outcomes. Our findings emphasize the critical importance of conducting splicing analysis within the broader genomic sequence context of the study gene and highlight the inherent uncertainties associated with intermediate SpliceAI scores (0.20 to 0.80). This study contributes to the field by being the first to prospectively interpret all potential coding SNVs in a disease-associated gene with a high degree of accuracy, representing a meaningful attempt at shifting from retrospective to prospective variant analysis in the era of exome and genome sequencing.

Association of Plasma YKL-40 With MRI, CSF, and Cognitive Markers of Brain Health and Dementia.

Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored the utility of plasma YKL-40 as a biomarker for accelerated brain aging and dementia risk. We performed cross-sectional and prospective analyses of 4 community-based cohorts in the United States or Europe: the Age, Gene/Environment Susceptibility-Reykjavik Study, Atherosclerosis Risk in the Communities study, Coronary Artery Risk Development in Young Adults study, and Framingham Heart Study (FHS). YKL-40 was measured from stored plasma by a single laboratory using Mesoscale Discovery with levels log transformed and standardized within each cohort. Outcomes included MRI total brain volume, hippocampal volume, and white matter hyperintensity volume (WMHV) as a percentage of intracranial volume, a general cognitive composite derived from neuropsychological testing (SD units [SDU]), and the risk of incident dementia. We sought to replicate associations with dementia in the clinic-based ACE csf cohort, which also had YKL-40 measured from the CSF. Meta-analyses of MRI outcomes included 6,558 dementia-free participants, and for analysis of cognition, 6,670. The blood draw preceded MRI/cognitive assessment by up to 10.6 years across cohorts. The mean ages ranged from 50 to 76 years, with 39%-48% male individuals. In random-effects meta-analysis of study estimates, each SDU increase in log-transformed YKL-40 levels was associated with smaller total brain volume (β = -0.33; 95% CI -0.45 to -0.22; p < 0.0001) and poorer cognition (β = -0.04; 95% CI -0.07 to -0.02; p < 0.01), following adjustments for demographic variables. YKL-40 levels did not associate with hippocampal volume or WMHV. In the FHS, each SDU increase in log YKL-40 levels was associated with a 64% increase in incident dementia risk over a median of 5.8 years of follow-up, following adjustments for demographic variables (hazard ratio 1.64; 95% CI 1.25-2.16; p < 0.001). In the ACE csf cohort, plasma and CSF YKL-40 were correlated (r = 0.31), and both were associated with conversion from mild cognitive impairment to dementia, independent of amyloid, tau, and neurodegeneration status. Higher plasma YKL-40 levels were associated with lower brain volume, poorer cognition, and incident dementia. Plasma YKL-40 may be useful for studying the association of inflammation and its treatment on dementia risk.

Associations between muscle dysmorphia symptomatology and sleep duration and difficulty in the Canadian Study of Adolescent Health Behaviors

ObjectivesPrior research has shown links between mental health symptomatology and poor sleep. However, associations between muscle dysmorphia symptomatology and poor sleep remain unknown, which was the aim of this study. MethodsData from the Canadian Study of Adolescent Health Behaviors (2021-2022) were analyzed (N = 912). Multinomial logistic regression analyses and logistic regression analyses were used to determine the association between muscle dysmorphia symptomatology and average sleep duration (5 hours or less, 6 hours, 7 hours, and 8 or more hours) and difficulty falling or staying asleep over a 2-week period. ResultsFindings indicated significant associations between muscle dysmorphia symptomatology and shorter sleep duration and greater sleep difficulty in both cross-sectional and prospective analyses. ConclusionsThe findings from this study underscore poor sleep as a correlate of muscle dysmorphia symptomatology among adolescents and young adults, emphasizing the need for screening and interventions in healthcare settings.

Effect of traditional rehabilitation programme versus telerehabilitation in adolescents with idiopathic scoliosis during the COVID-19 pandemic: a cohort study.

Telerehabilitation has become increasingly popular since the SARS-CoV-2 (COVID-19) outbreak. However, studies are needed to understand the effects of remote delivery of spine treatment approaches. To verify and compare the effects of traditional rehabilitation programmes (in-person) and telerehabilitation (online) on the progression of scoliotic curvature in adolescents with idiopathic scoliosis during the COVID-19 pandemic, and to verify the acceptability, appropriateness, and feasibility among patients and physiotherapists regarding both treatments. This is a cohort study (prospective analysis of 2 intervention groups: telerehabilitation (online) and traditional rehabilitation (in-person). A total of 66 adolescents with idiopathic scoliosis were included. Recruitment was conducted through the Clinical Center in Scoliosis Care (January-December 2020). Participants were divided into 2 intervention groups: telerehabilitation (online) (n=33) and traditional rehabilitation programme (in-person) (n=33). Both groups also were supplied with a spinal orthopaedic brace. Scoliosis was confirmed by a spine X-ray examination (Cobb angle). Radiographic parameters measured were: Cobb angles (thoracic and lumbar). The method of Nash and Moe (thoracic and lumbar) was also evaluated based on the relationship between the vertebral pedicles and the centre of the vertebral body in the X-rays. Assessments were performed at baseline (T0) and after 6 months of the intervention protocol (T6). Patient and physiotherapist reports were evaluated on the acceptability, appropriateness, and feasibility of the interventions. Adolescents with idiopathic scoliosis showed a significant decrease in the Cobb angle (main scoliotic curvature), with a 4.9° for the traditional rehabilitation programme and 2.4° for the telerehabilitation. Thoracic and lumbar Cobb angles did not show significant changes after the intervention in both groups or between groups. Thoracic and lumbar Nash and Moe scores scores also did not show significant differences after 6 months of in-person or telerehabilitation intervention, or between groups. The intervention by telerehabilitation was acceptable, appropriate, and feasible for patients and physiotherapists. Use of the rehabilitation programme for adolescents with idiopathic scoliosis, delivered via telerehabilitation during the COVID-19 pandemic, was encouraging for future applications due to the improved effect on reducing the Cobb angle, preventing progression of scoliosis. In addition, telerehabilitation showed good acceptability among patients and physiotherapists. Traditional rehabilitation programmes (in-person) in adolescents with idiopathic scoliosis also showed a reduction in the Cobb angle.

Demographics aspects of brain and spine metastatic melanoma. Retrospective analysis in a single third-level center

BackgroundMelanoma metastases to the CNS rank third in frequency, just after lung and breast metastases. There is controversy regarding the factors predisposing to developing CNS metastases in patients with cutaneous melanoma and their survival with conventional treatments. MethodsWe carried out a retrospective analysis in a third-level hospital in Mexico to determine epidemiological aspects of melanoma metastases to the central nervous system, factors related to its appearance, clinical presentation, and survival in three treatment groups: surgery, radiotherapy, and conservative management. ResultsWe found that the nodular variant has the most significant association with CNS metastases. In addition, the superficial spreading variant has the highest risk of presenting a more substantial number of lesions, up to seven for each case and predominantly in the infratentorial space. On the other hand, we found more remarkable survival in patients treated only with surgery than those treated with radiotherapy or conservatively. ConclusionsThis study lays the foundations for future prospective survival analysis of the different current treatment modalities for metastatic melanoma in the brain and spine. It also highlights the clinical risk factors for metastatic brain and spine tumors of melanoma.

Association between leisure sedentary behaviors and hypertension risk: A prospective cohort study and two-sample Mendelian randomization analysis in Europeans

ObjectiveThis study aimed to investigate the potential causal relationship between domain-specific sedentary behaviors (including television watching, computer use, and driving) and hypertension risk in European populations. MethodsInitially, we conducted a multivariable Cox regression analysis to evaluate the associations between domain-specific sedentary behaviors and the risk of developing hypertension using data from 261,829 hypertension-free participants in the UK Biobank. To validate the findings of observational analysis, we employed two-sample univariable mendelian randomization (UVMR) analysis utilizing summary statistics from genome-wide association study conducted on European populations. We then performed multivariable mendelian randomization (MVMR) analysis to account for the influence of the risk factors for hypertension. ResultsIn this prospective observational analysis, individuals who spent >3 h per day watching television had significantly higher risk of developing hypertension (HR = 1.24, 95% CI: 1.20–1.29, P < 0.001) compared to those who watched television for 0–1 h per day. The mendelian randomization analysis provided consistent evidence for a causal relationship between prolonged television watching time and hypertension risk (OR = 1.45, 95% CI: 1.25–1.69, P < 0.001; all PMVMR < 0.05) in both UVMR and MVMR results. No significant associations were found between computer use, driving behaviors and the risk of hypertension in either the observational or UVMR/MVMR analyses. ConclusionsThese findings provide evidence for a causal effect specifically linking higher television watching time to an increased risk of hypertension and indicate the potential effectiveness of reducing television viewing time as a preventive measure to mitigate the risk of hypertension.

Predictive accuracy of Barrett TK toric calculator compared to measured posterior corneal astigmatism using Pentacam in toric IOL power calculation.

To compare the predictive accuracy of Barrett total keratometry (Barrett TK) toric calculator with the measured posterior corneal astigmatism (PCA) by using Pentacam in toric intraocular lens (IOL) power calculation. A prospective analysis was done on 118 eyes requiring toric IOL power implantation. The absolute prediction error of the Barrett TK toric calculator and the measured PCA in the online toric calculator were assessed and compared to the standard Alcon toric calculator (with Barrett toric calculator incorporated). The mean absolute prediction error of the online toric calculator (0.32 D) (with Barrett toric calculator incorporated), Barrett TK Toric (0.34 D), and measured PCA of Pentacam in Barrett toric calculator (0.33 D) were found to be similar with no statistically significant difference. Subanalysis in eyes with with-the-rule astigmatism, against-the-rule astigmatism, and oblique astigmatism showed similar results. Alpins analysis showed that all three methods overcorrected corneal astigmatism. The Barrett TK toric calculator and the measured PCA of Pentacam in the Barrett toric calculator have similar predictive accuracy to the online toric calculator (with Barrett toric calculator incorporated).

Circulatory levels of lysophosphatidylcholine species in obese adolescents: Findings from cross-sectional and prospective lipidomics analyses

Background and aimsObesity has reached epidemic proportions, emphasizing the importance of reliable biomarkers for detecting early metabolic alterations and enabling early preventative interventions. However, our understanding of the molecular mechanisms and specific lipid species associated with childhood obesity remains limited. Therefore, the aim of this study was to investigate plasma lipidomic signatures as potential biomarkers for adolescent obesity. Methods and resultsA total of 103 individuals comprising overweight/obese (n = 46) and normal weight (n = 57) were randomly chosen from the baseline ORANGE (Obesity Reduction and Noncommunicable Disease Awareness through Group Education) cohort, having been followed up for a median of 7.1 years. Plasma lipidomic profiling was performed using the UHPLC-HRMS method. We used three different models adjusted for clinical covariates to analyze the data. Clustering methods were used to define metabotypes, which allowed for the stratification of subjects into subgroups with similar clinical and metabolic profiles. We observed that lysophosphatidylcholine (LPC) species like LPC.16.0, LPC.18.3, LPC.18.1, and LPC.20.3 were significantly (p < 0.05) associated with baseline and follow-up BMI in adolescent obesity. The association of LPC species with BMI remained consistently significant even after adjusting for potential confounders. Moreover, applying metabotyping using hierarchical clustering provided insights into the metabolic heterogeneity within the normal and obese groups, distinguishing metabolically healthy individuals from those with unhealthy metabolic profiles. ConclusionThe specific LPC levels were found to be altered and increased in childhood obesity, particularly during the follow-up. These findings suggest that LPC species hold promise as potential biomarkers of obesity in adolescents, including healthy and unhealthy metabolic profiles.

GJ Express: an improvement initiative to decrease sedation and anesthesia for gastrojejunostomy tube exchanges.

Overuse of sedation and anesthesia causes delays in gastrojejunostomy tube (GJ) exchanges, increased risk of complications, unnecessary use of resources, preventable hospital admissions, and an adverse impact on patient and family experience. Our hospital was over-utilizing sedation and anesthesia, and we aimed to decrease this use from 78% to 20% within two years. An interdisciplinary quality improvement team comprehensively evaluated current processes for GJ tube exchanges through a retrospective chart review for baseline data with prospective time series analysis after improvement implementation. The primary outcome measure was the percentage of pediatric patients that utilized sedation or anesthesia for routine GJ tube exchanges. A statistical process control p-chart was used to calculate and show changes over time for patients (n = 45 patients average). The median percent of pediatric GJ tube exchanges performed with sedation or anesthesia decreased from 77.8% to 11.3%. Most patients (76%) were covered by Medicaid programs; with low reimbursement rates, decreased anesthesiologist billing revenue does not have a negative financial impact. An interprofessional improvement initiative that engaged patients and families, incorporated pediatric-specific staff services, and developed systematic weaning was associated with a significant decrease in the overuse of sedation and anesthesia for GJ tube exchanges. We believe that this work is highly relevant and impactful for medical centers caring for children who require gastrojejunostomy tubes, an increasingly common approach to management of children with feeding issues. There is very little literature available on the use of sedation or anesthesia for changing these tubes. While large children's medical centers in the USA usually do not utilize sedation or anesthesia, there are likely many serious outliers, especially when children receive care outside of a pediatric specific institution. This paper brings awareness to this serious issue and provides information about how we changed care to achieve higher patient safety and lower medical costs.

Sustainability of Integrated Farming Between Robusta Coffee and Goat Livestock in Pupuan District, Tabanan Regency

Purpose of this research was to analyze actual income, optimize income and analyze the sustainability of integrated farming between Robusta coffee and goat farming in Pupuan District, Tabanan Regency. Location of research was determined purposive with several considerations. The research sample was 30 farmers plus seven experts. Data collected using in-depth interviews, surveys with questionnaires, browsing through the internet, literature studies, farmers' notes and reports from related agencies. Data analysis using Gross Margin analysis, Linear Programming with the help of BLPX88 Software, Multidimensional Scaling (MDS) with RAP-Farm approach, and Participatory Prospective analysis. Based on the research results, it is known that the average actual income of farmers from integrated farming between Robusta coffee and goat livestock is Rp 19.179.508,00 a year or Rp 1.598.292,00 a month. Optimizing the income of all farmers with a cultivated land area of 23.01 ha, it is stated that farming is carried out optimally with a maximum income of IDR 492.081.500,00 a year. An increase of Rp 29.033.405,00 or 6.27% a year from the gross margin value of Rp 463,048,095.00 a year. The sustainability status of all dimensions is stated to be quite sustainable with an index value of 64.73. Based on the Participatory Prospective analysis, it is known that the factors that most influence on sustainability are altitude, farmer's education level, climate conditions, government policy, availability of production inputs, frequency of extension and training of farmers, farmer's knowledge, coordination with institutions/agencies, availability of production facilities, availability of farmer capital. It can be suggested that farmers' income needs to be increased again by using the right farming technology. To maximize farming income, farmers should use labor in families that are still large. It is necessary to increase the index value and status of sustainability in all dimensions through intervention on the most influential key factors.

Escherichia coli and HPV16 coinfection may contribute to the development of cervical cancer

ABSTRACT Persistent human papillomavirus HPV infection is a necessary but insufficient condition for cervical cancer. Microorganisms are crucial environmental factors in cancers susceptibility and progression, recently attracting considerable attention. This study aimed to determine the infection status and relationship between high-risk HPV (HR-HPV) and lower genital tract infectious pathogens in cervical cancer and its precursors. From a retrospective and a prospective cohort analysis, Escherichia coli (E. coli) dominated the pathogens isolated from cervical discharges, and an isolation rate uptrend has been shown recently. HPV16 and E. coli’s coinfection rate gradually increased with the severity of cervical intraepithelial neoplasia. The adhesion and invasion abilities of the isolated E. coli to HPV16-positive SiHa cells were evaluated in vitro. The TCGA database and cervical tissues samples analysis showed that IL-10 was upregulated in cervical cancer. IL-10 expression levels increased in tissue samples with the severity of cervical cancer and its precursors with HPV16 and E. coli coinfection. Although no significant changes in IL-10 production were observed in the co-culture supernatant, we hypothesized that Treg immune cells in the tumour microenvironment might be responsible for the local IL-10 upregulation, according to our data showing Foxp3 upregulation and an upward trend with the cervical intraepithelial neoplasia grading to cancer and tumours with E. coli and HPV16 coinfection. Our data provide insights into the possible role of E. coli in cervical cancer progression and suggest that the application of HPV and E. coli screening programs may be an effective strategy to relieve the burden of cervical cancer and its precursor lesions.

Multimodal prehabilitation in elective oncological colorectal surgery enhances preoperative physical fitness: a single center prospective real-world data analysis.

Surgery can lead to curation in colorectal cancer (CRC) but is associated with significant morbidity. Prehabilitation plays an important role in increasing preoperative physical fitness to reduce morbidity risk; however, data from real-world practice is scarce. This study aimed to evaluate the change in preoperative physical fitness and to evaluate which patients benefit most from prehabilitation. In this single-arm prospective cohort study, consecutive patients undergoing elective colorectal oncological surgery were offered a 3- to 4-week multimodal prehabilitation program (supervised physical exercise training, dietary consultation, protein and vitamin supplementation, smoking cessation, and psychological support). The primary outcome was the change in preoperative aerobic fitness (steep ramp test (SRT)). Secondary outcomes were the change in functional walking capacity (6-minute walk test (6MWT)), and muscle strength (one-repetition maximum (1RM) for various muscle groups). To evaluate who benefit most from prehabilitation, participants were divided in quartiles (Q1, Q2, Q3, and Q4) based on baseline performance. In total, 101 patients participated (51.4% male, aged 69.7 ± 12.7 years). The preoperative change in SRT was +28.3 W, +0.36 W/kg, +16.7% (P<0.001). Patients in all quartiles improved at the group level; however, the relative improvement decreased from Q1-Q2, Q2-Q3, and Q3-Q4 (P=0.049). Change in 6MWT was +37.5 m, +7.7% (P<0.001) and 1RM improved with 5.6-33.2 kg, 16.1-32.5% for the various muscle groups (P<0.001). Prehabilitation in elective oncological colorectal surgery is associated with enhanced preoperative physical fitness regardless of baseline performance. Improvements were relatively larger in less fit patients.

Prospective modelling of operational offshore wind farms on the distribution of marine megafauna in the southern North Sea

Intense development of Offshore Wind Farms (OWFs) has occurred in the North Sea with several more farms planned for the near future. These OWFs pose a threat to marine megafauna stressing the need to mitigate the impact of human activities. To help mitigate impacts, the Before After Gradient (BAG) design was proposed. We explored the use of the BAG method on megafauna sightings recorded at different distances from OWFs in the southern North Sea. We predicted intra-annual variability in species distribution, then correlated species distribution with the presence of operational OWFs and investigated the potential impact the operation of prospective OWFs may have on species distribution. Four patterns of intra-annual variability were predicted: species most abundant in spring, in winter, in both spring and winter, or all year round. We recommend that future OWF constructions be planned in summer and early fall to minimise impact on cetaceans and that offshore areas off northern France and Belgium be avoided to minimise impact on seabirds. Our prospective analysis predicted a decreased density for most species with the operation of prospective OWFs. Prospective approaches, using e.g. a BAG design, are paramount to inform species conservation as they can forecast the likely responses of megafauna to anthropogenic disturbances.