Arm Group Research Articles

Effects of Eccentric Exercise of the Extensors on Eccentric Exercise-Induced Muscle Damage of the Flexors in Limbs.

We tested the hypothesis that muscle damage protection effect would be induced by its antagonist muscle eccentric exercise. Sedentary young (20-28y) men were randomly assigned into six groups; three groups each for arm or leg exercise group (n = 12/group). One group performed two bouts of 30 maximal eccentric contractions (30MaxEC) of the elbow flexors (EF) or 60 maximal eccentric contractions (60MaxEC) of the knee flexors (KF) using a different arm (contra-EF-EF) or leg (contra-KF-KF) between bouts. The other two groups performed 30MaxEC of the elbow extensors (EE) or 60MaxEC of the knee extensors (KE) first followed by the 30MaxEC of EF or 60MaxEC of KF using the ipsilateral (ipsi-EE-EF, ipsi-KE-KF) or contralateral limb (contra-EE-EF, contra-KE-KF). The two exercise bouts were separated by 2 weeks for all groups. Changes in muscle damage markers before to 5 days following exercise were compared among the groups by mixed-design two-way ANOVAs. Changes in the markers following the second bout of the ipsi-EE-EF, contra-EE-EF, ipsi-KE-KF, and contra-KE-KF groups were smaller (P < 0.05) than those after the first bout of the contra-EF-EF and contra-KF-KF groups, respectively. The changes after the second bout were smaller (P < 0.05) for the ipsi-EE-EF than contra-EE-EF, and ipsi-KE-KF than contra-KE-KF group; however, those in the contra-EE-EF and contra-KE-KF groups were larger (P < 0.05) than those following the second bout of the contra-EF-EF and contra-KF-KF groups. These results showed that the magnitude of muscle damage of EF or KF was reduced by the initial bout of EE or KE eccentric exercise performed by both ipsilateral and contralateral limbs, suggesting that muscle damage protective effect is conferred by the antagonist muscle in the same and opposite limbs.

A comparative study of modified Bassini's repair and lichtenstein repair for indirect inguinal hernia in young age population

Background: Inguinal hernia surgery has significant world-wide diversity in management. European Hernia Society guidelines 2020, for management of groin hernias recommends the use of open non-mesh repair in specific patients or types (e.g. young males with lateral hernia)as an acceptable alternative to a Lichtenstein technique. The present study deals with the comparison of intra operative, postoperative course and clinical outcome of modified bassinis repair (non mesh) and Lichtenstein repair [mesh repair] for indirect inguinal hernia in young age population. Methods: Observational analytical prospective cohort study, conducted in General Surgery, Peoples hospital, Bhopal from November 2022 to February 2024. Patient of indirect inguinal hernia in the age (16-35 years) group and operated by either Modified Bassinis (Group A, n=34) or lichtenstein hernia repair (Group B, n=48). The above study arms group were studied and compared. Results: Mean duration of surgery among Group A patients was 62.65 minutes and 57.19 minutes in Group B. Seropurulent discharge among 2.9% patients in Group A and 4.2% in Group B and superficial SSI among 2.9% patients in Group A and 4.2% in Group B was reported. Chronic post-operative pain VAS score was assessed at end of 2nd week, end of 1 month and end of 3 months with statistically no significant among two groups. Conclusions: Our study did not demonstrate any significant difference of one repair method over the other. However, an Individualized approach for cases with a customized strategy is recommended for surgical management of hernia.

Confronting Rifles with Words: The High Islamic Council of Mali and Non-State Armed Groups

Abstract Since the 2012 Tuareg rebellion and the takeover of large areas in the north of Mali by Islamic fundamentalist groups, Muslim religious leaders in the country have spearheaded important negotiation initiatives under the auspices of the High Islamic Council of Mali (HCIM). On more than one occasion, these initiatives have led to the liberation of detainees or the possibility of humanitarian convoys reaching communities caught in the midst of the armed conflict. Why were these initiatives successful (or unsuccessful)? How did religious leaders convince non-state armed groups to adopt conduct that complies with basic humanitarian norms? Drawing on desk-based and fieldwork research conducted as part of the Generating Respect Project, this article seeks to answer these questions and to identify the endogenous and contextual factors that contributed to the successes of the HCIM and its negotiators.

Thienyltriazine Triamides: Thickness Insensitive Interlayer Materials Featuring Fine-Tuned Optoelectronic and Aggregation Characters for Efficient Organic Solar Cells.

A novel class of thienyltriazine triamides (TTTAs) was facile synthesized and firstly used as cathode interlayers (CILs) for organic solar cells (OSCs). By utilizing different aromatic arms and pendant polar groups, their optoelectronic properties and aggregation behaviors were effectively modulated. The combination of thienyltriazine (TT) core, naphthylamide arm and imidazole pendant group endows TT-N-M with suitable energy levels, intensified work function tunability, higher conductivity, and well-balanced crystallinity and film-forming ability, boosting both the performance and stability of OSCs significantly. Remarkably, the solar cell efficiency remains stable at around 90 % of the optimal efficiency even as the interlayer thickness varied from 5 to 95 nm, demonstrating its insensitivity to thickness. Moreover, TT-N-M exhibits compatibility with various active layer systems, achieving a maximum efficiency of 19.60 % for single-junction solar cell. Its exceptional tolerance to thickness fluctuations and performance establishes a new benchmark for multi-armed CIL-based OSCs, also positioning them among the most high-performing CIL materials documented thus far. This work not only broadens the scope of CIL materials for OSCs but also offers deep insights into design strategies and structure-properties relationships, being beneficial for the future development of more efficient CIL materials for organic optoelectronic applications.

Implicit motor sequence learning using three-dimensional reaching movements with the non-dominant left arm

Interlimb differences in reach control could impact the learning of a motor sequence that requires whole-arm movements. The purpose of this study was to investigate the learning of an implicit, 3-dimensional whole-arm sequence task with the non-dominant left arm compared to the dominant right arm. Thirty-one right-hand dominant adults completed two consecutive days of practice of a motor sequence task presented in a virtual environment with either their dominant right or non-dominant left arm. Targets were presented one-at-a-time alternating between Random and Repeated sequences. Task performance was indicated by the time to complete the sequence (response time), and kinematic measures (hand path distance, peak velocity) were used to examine how movements changed over time. While the Left Arm group was slower than the Right Arm group at baseline, both groups significantly improved response time with practice with the Left Arm group demonstrating greater gains. The Left Arm group improved performance by decreasing hand path distance (straighter path to targets) while the Right Arm group improved performance through a smaller decrease in hand path distance combined with increasing peak velocity. Gains made during practice on Day 1 were retained on Day 2 for both groups. Overall, individuals reaching with the non-dominant left arm learned the whole-arm motor sequence task but did so through a different strategy than individuals reaching with the dominant right arm. The strategy adopted for the learning of movement sequences that require whole-arm movements may be impacted by differences in reach control between the nondominant and dominant arms.

Combination of carvedilol with variceal band ligation in prevention of first variceal bleed in Child-Turcotte-Pugh B and C cirrhosis with high-risk oesophageal varices: the ‘CAVARLY TRIAL’

ObjectivesBeta-blockers and endoscopic variceal band ligation (VBL) have been preferred therapies for primary prophylaxis of variceal bleeding. However, the choice of therapy in patients with advanced liver disease with high-risk...

Initiated Breastfeeding and Physiological Patterns in Newborn Infants When Reunited With Mother After Separation Due to Elective Cesarean Birth.

The purpose of this study was to compare the effects of two caregiving models on full-term healthy infants' wakefulness, rooting and sucking reflexes, initiation of breastfeeding, and physiological parameters when reunited with their mothers after a mother-infant separation of 130 min after elective cesarean birth. Ninety-five mother-infant pairs participated in a randomized controlled trial, in which full-term healthy infants were allocated to be either dressed in their mothers' arms (n = 56) or skin-to-skin with their mother (n = 39) when reunited with the mother within 130 min after cesarean birth. Data were collected by the Neonatal Behavioral Assessment Scale (NBAS) to assess the infants' wakefulness and prebreastfeeding behaviors. Physiological parameters were assessed at 15 min intervals, from 130 to 205 min after birth. Time to first breastfeed was measured in minutes from the reunion with the mother. The primary finding was that physiologic parameters did not differ but time for initiation of breastfeeding after the reunion with the mother was significantly faster in the skin-to-skin group compared to the infants in the mothers' arms group (p = 0.005). Over the full study period, a more relaxed state and drowsy were found in the skin-to-skin group compared to the infants in the mothers' arms group. Healthy full-term infants born by elective cesarean, who were cared for by their mothers when reunited within 130 min of separation and cared for by their fathers during the mother-infant separation, initiated breastfeeding successfully and showed stable physiological patterns.

Petrochemical and geochronological constraints on the origin of the Sops Arm group, the most westerly Silurian volcano-sedimentary extensional basin on the western Newfoundland composite Laurentian margin

Petrochemical and geochronological constraints on the origin of the Sops Arm group, the most westerly Silurian volcano-sedimentary extensional basin on the western Newfoundland composite Laurentian margin

Management of white spot enamel lesions with resin infiltration: potentials and future research directions.

The current study1 is a randomized controlled trial with two arm, multicenter and parallel group design. Study subjects were 38 orthodontic patients younger than 17 years who were being treated with metal braces. Patients with at least one white spot lesion (WSL) graded 1 to 2 according to the International Caries Detection and Assessment System (ICDAS) on the labial surface of permanent maxillary and mandibular canines and incisors were included for the trial. Teeth with carious lesions and restorations, anomalies of the enamel, and primary teeth were excluded. Patients were allocated by computer generated random sequence into resin infiltration and fluoride varnish intervention groups. Study subjects were blinded until the allocation, outcome assessors and statisticians remained blinded through the study, however the operators could not be blinded. Resin infiltration treatment involved removal of orthodontic wires and auxiliaries followed by cleaning the teeth with fluoride free prophylactic paste and completing the resin infiltration according to manufacturer's instructions. In the fluoride varnish group, a thin layer of the material was applied after isolating the teeth, and patients were asked not to eat or drink for 1 hour. This was continued twice a month for 6 months. Digital images of the teeth were obtained before, and 1 day (T1), 1 week (T2), 1 month (T3), 3 months (T4) and 6 months (T5) after treatment, using a DSLR camera and a matching polarization filter. The images were processed for calibration and color stability. Regions of interest representing WSL (white spot lesion) and SAE (sound adjacent enamel) were isolated in the images for comparison at different stages the images were captured. Statistical analysis was performed using SPSS version 28. Independent-samples t-test was utilized for comparison between the two groups, and paired-samples t-test for comparison within the groups. A statistical significance level of α = 0.05 was set. At T1, significant color difference was observed between white spot lesion and adjacent sound enamel in the resin infiltration group and it remained stable after 6 months. Whereas in the fluoride varnish group, there were no statistical differences from baseline to 6 months. A statistical difference of 3.27 CIELAB units (p < 0.001) was reported between the infiltration group and the fluoride group at T5. No significant changes were noted in SAE with respect to changes in lightness. Resin infiltration was found to be better at masking the demineralization produced by WSL and also enhanced the esthetic appearance of demineralized areas around the brackets. Resin infiltration did not produce any clinically visible effects in non-affected enamel. These changes remained stable for a period of 6 months.

Bombs and Banners: Battlefield Dynamics and Armed Groups’ Use of Nonviolent Tactics in Civil War

Under what circumstances do armed insurgents divert scarce resources to nonviolent tactics? Despite extensive research on the causes and consequences of civil wars and resistance campaigns, our understanding of when rebel organizations add nonviolent tactics to their repertoire is limited. Moving beyond traditional explanations of nonviolent resistance campaigns, we hypothesize that rebel organizations use nonviolent tactics–such as strikes and protest–to capitalize on successes on the battlefield. Rebels have many incentives to use nonviolent tactics, but their opportunity to do so typically depends on their ability to mobilize civilians. Military successes help pave the way for mobilization by shifting civilians’ expectations about the prospects for victory and repression. Using cross-national data on rebel nonviolent contention, including original data on nonviolent tactics in struggles for control over the central government, we find robust support for our argument. Probing potential scope conditions, we show that the association is strongest among rebel organizations with civilian wings and for rebels fighting for control over the government. Our findings provide new insight into the full array of tactics that insurgents deploy, beyond variations in armed activity. They contribute to our understanding of the many forms that contentious action can take, even amidst a backdrop of violence.

Internal and External Rotators Muscle Strength Ratio and Acromio-Humeral Distance as Predictors of Shoulder Injuries in Volleyball Players

Abstract Purpose We aimed to investigate the ratio between strength of internal and external rotators of shoulder using handheld dynamometer and acromio-humeral distance actively and passively using musculoskeletal ultrasound to identify a relation between strength imbalance and shoulder joint injuries in Egyptian volleyball players. Methods A case control study, carried out on 60 volleyball players, subdivided into 2 subgroups, 30 with shoulder pain (injured group) and 30 apparently healthy players as a control group. The internal and external rotator muscles were measured with and held dynamometer, and acromio- humeral distance was measured using musculoskeletal ultrasound. Results injured group included 10 female players (33.3%) and 20 male players (66.7%), age ranged between 16-30 years old, while control group included 4 females (13.3%) and 26 males (86.7%). Internal and external rotation strength ratio was less than 0.9 in injured group in the dominant arm, in favor of the normal group with statistical difference between them (p &amp;lt; 0.004). Acromio-humeral distance actively in injured group ranged from 0.45 to 0.87cm with mean ±SD of (0.64±0.07), less than normal group which ranged from 0.7 to 1cm with a mean ±SD of (0.79±0.08) (p &amp;lt; 0.000) Conclusion Weakness of external rotators muscles strength will decrease ratio between external rotator/internal rotator muscles, reducing the acromio-humeral distance especially during abduction, leading to shoulder injuries among volleyball players.

Financial incentives for sanitation take-up: A randomized control trial in rural Vietnam

This study assesses the impact of financial incentives on hygienic latrine ownership by poor/near-poor households in Vietnam. Rural communes were randomly assigned to a control group and three treatment arm groups: (T1) a rebate for households that installed a hygienic latrine; (T2) a financial reward for commune governments if the proportion of hygienic latrines in their commune increased by 30 percentage points; (T3) both a household rebate and a commune reward. We find a strong and positive effect from the household rebate (treatment arms 1 and 3) but an insignificant effect from the commune reward (treatment arm 2) on household ownership of a septic tank latrine. Our analysis provides suggestive evidence that microcredit is a channel through which a rebate encourages the installation of septic tank latrines. We also find that treatment arm 3 increases people's knowledge regarding sanitation and the availability of water and soap for handwashing within households.

Design and Parameter Optimization of Rotary Double-Insertion Device for Small Arched Insertion Machine

China’s small arched shed-building machinery suffers from a low degree of mechanization, building efficiency, and qualification rate for frame insertion. Therefore, we designed a rotary double-insertion device and established the equation for its motion trajectory. The analysis shows that in the rotary insertion process, a better point of entry into the soil exists. A simulation model was constructed in ADAMS, and the static and dynamic trajectories were analyzed. Additionally, the optimal planting and insertion speed ratios were determined. Considering the qualified rate of the insertion frame as the evaluation index to establish a regression model, we adopted a three-factor three-level experimental design and established the planting speed ratio, center distance of the planting arm, and length of the pressing rod arm as the main influencing factors. We used Design-Expert 13 to perform the analysis of variance and determined the optimal parameter combinations. The experimental results show that the planting speed ratio was 0.7, the center distance of the planting arm group was 554 mm, the length of the pressing rod arm was 923 mm, and the qualification rate of trellis planting at this time was 98.05%. The bench was adjusted and tested based on the optimal parameter combination. The average value of the measured trellis qualification rate was 96.73%, and the relative error between the test value and the theoretical optimization value was 1.32%, thereby verifying the reliability of the optimal parameter combination. Field verification test results show that the rotary double-insertion device had a planting speed ratio of 0.7 and a trellis qualified rate of 95.74% compared with the theoretical optimization value of 2.31%. Conforming to the design requirements of small arch shed-building machinery, the prototype operation performance was stable.

Efficacy of human milk fortification in low-birth-weight infants; A randomized controlled trial

Introduction: Low Birth Weight (LBW), less than 2500grams, has significant effect on baby survival and growth. A good supportive care in addition to breastfeeding is very important. Breast milk fortification role is under research. Aims; To study the Efficacy of Human Milk Fortification in Low-Birth-Weight Infants Materials and Methods: This RCT was conducted at Department of pediatrics Lady Reading Hospital, Peshawar, Pakistan, from October 2021 to March 2022. A total of 60 low birth weight neonates were randomly allocated into two arms (group A fortified) and (group B unfortified) through non probability consecutive sampling technique. One group was given fortified expressed breast milk with 1g sachet of Human Milk Fortifier (HMF). The second group was fed with unfortified breast milk only. Babies were monitored every two-weekly with Biochemical markers. Data was analyzed through descriptive and inferential means using independent T Test. Results: The mean weight of neonates in the supplemented group was 2273.83g (Mean SD = 2273.83g 182.83g) and in the control group it was 2176.67g (Mean SD = 2176.67g 181.86g). Result shows that infants given human milk fortifier gain more weight as compared to breast milk. Statistical analysis also showed significant difference (P value 0.017) Conclusion: It is concluded that use of human fortified milk is helpful in gaining weight in low birth weight infants. It also improves serum calcium and protein levels.

Add-on Vitamin E in Improving Treatment Outcomes in Diabetic Peripheral Neuropathy: A Prospective Interventional Study

Background: Neuropathy is one of the most common long-standing complications of diabetes, affecting over 50% of the diabetic individuals. Managing DPN and its complications involves comprehensive care and a multidisciplinary approach. Besides pharmacological treatments, botanicals and dietary supplements that have also been found to improve symptoms of DPN without affecting glucose control. The possible role of vitamin E in the management of DPN have been postulated in various studies. The present study thus aimed to prospectively assess whether add-on treatment with vitamin E can improve treatment outcomes in diabetic peripheral neuropathy.Methods: The study included newly diagnosed patients with diabetic peripheral neuropathy for a period of initial two months. Patients were randomly allocated to either standard treatment Group (Group A) or the interventionGroup (Group B). As a part of intervention, patients received vitamin E 400mg once daily in addition to thestandard of care. Efficacy Parameters measured at baseline, 6 months and 12 months included changes in visual analog scoring, mean pain score, brief pain inventory and patient’s global impression of change. Treatment safety, quality of life and treatment adherence was assessed. Data was statistically analysed.Result: The study included a total of 100 patients, 50 patients in each Group. Significantly higher decrease of glycaemic measures was noted for Group B compared to Group A in terms of PPPG and serum creatinine, however, there was comparable change in HbA1c and FPG for both Groups. There was comparable significant reduction in mean VAS scoring at 6 and 12 months for Group B. Considering all the efficacy measures, there was highest reduction for the pain interference in the intervention arm (Group B), in comparison to Group A. (p&lt;0.001). Quality of life measures and mean adherence scoring significantly increased for treatment group B as compared to A at both 6 months and 12 months of study assessments. No major safety concerns were reported during the study period.Conclusion: Our study noted that addition of vitamin E as an added supplementation to the standard of careshowed benefits in terms of patient reported reduced pain interference and pain perception, which also significantly improved overall quality of life in these patients.

(070) Assessment the Efficacy of Daily Use of Duloxetine in Treatment of Premature Ejaculation: A Prospective Randomized Placebo-Controlled Cross Over Clinical Trial

Abstract Introduction Premature ejaculation is considered to be the most common male sexual disorder, affecting 5% to 40% of sexually active men. Duloxetine is a serotonin and norepinephrine reuptake inhibitor. •It inhibits the reuptake of serotonin and norepinephrine, combining two therapeutic mechanisms in one agent to treat depression and anxiety and also raises dopamine levels. Objective The aim of this study is evaluating the efficacy of “daily” use of Duloxetine in treatment of PE either primary or secondary. Methods •This Randomized Clinical Trial enrolled among (68) Male patients had Premature ejaculation (PE) diagnosed with quantification of the intra-vaginal ejaculation latency time (IELT) less than 2 minutes. •The (68) potent male patients complaining of PE were divided into two groups: - •Intervention arm Group (A): patients with PE either primary or secondary that received (duloxetine 30mg) daily for 1 month. •Control arm Group (B): patients with PE either primary or secondary that they received placebo treatment daily for 1 month Results A total of 68 patients were eligible for inclusion in the current study, they had a mean age of 38.4 ± 6.1 years, secondary premature ejaculation accounted for 91.2% of the included patients. Baseline IIEF-5 showed a median of 24 (range 22–33), median AIPE was 19 (range 8–30), median IELT 60 sec (range 30–120), median Male SQOL 20 (range 15–33). •All participants had a median AIPE was 26 (range 9–34), median IELT 180 sec (range 30–240), median Male SQOL 43 (range 18–55) after being treated with duloxetine. While median AIPE after placebo was 19 (range 8–30), IELT after placebo 60 seconds (30–160), Male SQOL after placebo was 21 (range 16–33). Conclusions •A daily dose of Duloxetine (30 mg) had an effective role in improving premature ejaculation (PE)severity and quality of life either primary or secondary regarding Disclosure No.

Morphological changes and hub genes screening in rats with anorectal malformations during hindgut development

BackgroundAnorectal malformations (ARMs) are among the most common congenital digestive tract malformations worldwide. Although there have been extensive efforts for elucidating their pathogenesis, the specific molecular mechanisms underlying ARMs remain unclear. MethodsWe generated ARM Wistar rat models using ethylenethiourea. Nine pregnant rats were allocated to the ARM and control groups, respectively. Hindgut tissue was isolated from embryos collected on gestational days 14, 15, and 16, representing the key timepoints of anorectal development. High-throughput sequencing was used to identify differentially expressed genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the obtained genes. Module analysis was performed via Search Tool for the Retrieval of Interacting Genes (STRING), and a protein-protein interaction (PPI) network was constructed using Cytoscape software. Gene Set Enrichment Analysis (GSEA) was conducted to verify the enrichment of development/apoptosis/epithelium/morphogenesis/Wnt pathway-related core gene sets and identify ARM hub genes. Reverse transcription-quantitative polymerase chain reaction assay was employed to verify mRNA levels of hub genes. Results313 GSEA core genes form ten core gene sets were selected. Based on the 281 differentially expressed circRNAs (|Fc| > 2, FDR < 0.05), 42 PPI core genes were obtained. According to the integration of GSEA analysis and PPI network, three hub genes (Cul1, Gli3, and Osr2) highly associated with ETU-induced ARMs were identified. The qRT-PCR validation data were consistent with the sequencing results. ConclusionsThese results provide a theoretical basis for the further identification of potential diagnostic and therapeutic targets in ARMs.

Contralateral second dose improves antibody responses to a 2-dose mRNA vaccination regimen.

BACKGROUNDVaccination is typically administered without regard to site of prior vaccination, but this factor may substantially affect downstream immune responses.METHODSWe assessed serological responses to initial COVID-19 vaccination in baseline seronegative adults who received second-dose boosters in the ipsilateral or contralateral arm relative to initial vaccination. We measured serum SARS-CoV-2 spike-specific Ig, receptor-binding domain-specific (RBD-specific) IgG, SARS-CoV-2 nucleocapsid-specific IgG, and neutralizing antibody titers against SARS-CoV-2.D614G (early strain) and SARS-CoV-2.B.1.1.529 (Omicron) at approximately 0.6, 8, and 14 months after boosting.RESULTSIn 947 individuals, contralateral boosting was associated with higher spike-specific serum Ig, and this effect increased over time, from a 1.1-fold to a 1.4-fold increase by 14 months (P < 0.001). A similar pattern was seen for RBD-specific IgG. Among 54 pairs matched for age, sex, and relevant time intervals, arm groups had similar antibody levels at study visit 2 (W2), but contralateral boosting resulted in significantly higher binding and neutralizing antibody titers at W3 and W4, with progressive increase over time, ranging from 1.3-fold (total Ig, P = 0.007) to 4.0-fold (pseudovirus neutralization to B.1.1.529, P < 0.001).CONCLUSIONSIn previously unexposed adults receiving an initial vaccine series with the BNT162b2 mRNA COVID-19 vaccine, contralateral boosting substantially increases antibody magnitude and breadth at times beyond 3 weeks after vaccination. This effect should be considered during arm selection in the context of multidose vaccine regimens.FUNDINGM.J. Murdock Charitable Trust, OHSU Foundation, NIH.

Constructing a finer-grained representation of clinical trial results from ClinicalTrials.gov

Randomized controlled trials are essential for evaluating clinical interventions; however, selective reporting and publication bias in medical journals have undermined the integrity of the clinical evidence system. ClinicalTrials.gov serves as a valuable and complementary repository, yet synthesizing information from it remains challenging. This study introduces a curated dataset that extends beyond the traditional PICO framework. It links efficacy with safety results at the experimental arm group level within each trial, and connects them across all trials through a knowledge graph. This novel representation effectively bridges the gap between generally described searchable information and specifically detailed yet underutilized reported results, and promotes a dual-faceted understanding of interventional effects. Adhering to the “calculate once, use many times” principle, the structured dataset will enhance the reuse and interpretation of ClinicalTrials.gov results data. It aims to facilitate more systematic evidence synthesis and health technology assessment, by incorporating both positive and negative results, distinguishing biomarkers, patient-reported outcomes, and clinical endpoints, while also balancing both efficacy and safety outcomes for a given medical intervention.

Development of thiacrown ligands for encapsulation of mercury-197m/g into radiopharmaceuticals.

The theranostic pair mercury-197m and mercury-197g (197m/gHg, t1/2 = 23.8 h/64.14 h), through their γ rays and Meitner-Auger electron emissions, have potential use as constituents in radiopharmaceuticals to treat small metastatic tumours. However, the use of this pair of nuclear isomers in radiopharmaceuticals requires the development of suitable [197m/gHg]Hg2+ chelators as currently there is a lack of established ligands for radiometals in the field. Herein, this work studies the natHg/197m/gHg coordination of three thiacrown 18-membered N2S4 macrocycles with pendant arms of varying chemical "softness". Following the synthesis and characterization of the N2S4 ligand series (6,6'-((1,4,10,13-tetrathia-7,16-diazacyclooctadecane-7,16-diyl)bis(methylene))dipicolinic acid (N2S4-Pa), 7,16-bis(pyridin-2-ylmethyl)-1,4,10,13-tetrathia-7,16-diazacyclooctadecane (N2S4-Py) and 7,16-bis(2-(methylthio)ethyl)-1,4,10,13-tetrathia-7,16-diazacyclooctadecane (N2S4-Thio)), Hg2+ complexes were studied through mass spectrometry, nuclear magnetic resonance (NMR) spectroscopy, and density functional theory (DFT) calculations, revealing successful complexation of all ligands with the Hg2+ ion. Radiolabeling studies demonstrated the effect of the pendant arm on [197m/gHg]Hg2+ coordination, as N2S4-Thio and N2S4-Py had the highest radiochemical yield, similar to that of previously reported N-benzyl-2-(1,4,7,10-tetrathia-13-azacyclopentadecan-13-yl)acetamide (NS4-BA), while N2S4-Pa had the lowest. The complex integrity of [197m/gHg][Hg(N2S4-Py)]2+ and [197m/gHg][Hg(N2S4-Thio)]2+ in both human serum and glutathione was notably lower compared to the [197m/gHg][Hg(NS4-BA)]2+ complex. However, the [197m/gHg][Hg(N2S4-Py)]2+ and [197m/gHg][Hg(N2S4-Thio)]2+ complexes remained above 70% intact over 82 h when competed against biologically relevant metals (ZnCl2, FeCl3, CuCl2, MgCl2 and CoCl2), suggesting the selectivity of the ligands for Hg2+. This study illustrates the importance of the macrocyclic backbone size and electron-donor groups of the donor pendant arms in the design of chelators for 197m/gHg-radiopharmaceuticals, as both affect the radiolabeling properties and complex inertness.