Presumptive Evidence Research Articles

Bisphenol-A and pentachlorophenol sodium levels in patients with rosacea

Background/ Objectives Rosacea is a common chronic inflammatory skin disorder. Endocrinedisrupting chemicals (EDC) are toxic substances, that may gain entry through the skin and subsequently interfere with hormonal and immune functions. Bisphenol A (BPA) and pentachlorophenol sodium (PCS) are two of these EDCs, incriminated in the pathogenesis of certain inflammatory skin disorders. We aimed to test the hypothesis that exposure to BPA and PCS might be involved in the pathogenesis of rosacea. Methods This prospective cross-sectional study involved 34 patients with rosacea (18F/16 M; mean age 48.5 ± 11 years) and 34 age and sex-matched healthy controls (20 F/14 M; mean age 48.2 ± 10.2 years). Main anthropometric measures, fasting plasma glucose (FPG), insulin, HOMA-IR, lipids, C-reactive protein (CRP), BPA, and PCS levels were quantified and recorded. Results Serum CRP (9.6 ± 3.4 vs. 3.7 ± 1.6 mg/L, respectively, p0.05 for all). Serum BPA levels were 55.8 ± 14.4 and 51.9 ± 19.2 ng/mL, and PCS levels were 63.3 ± 45.9 ng/mL and 68.6 ± 40.8 ng/mL for patients and healthy controls, respectively. There was no significant difference in BPA and PCS levels between the two groups (p > 0.05 for both). No significant association was found among HOMAIR, CRP, BPA, and PCS levels (p > 0.05 for all). Conclusions Although the present study fails to provide presumptive evidence for the role of BPA and PCS in rosacea, the question as to other EDCs might be involved in its etiopathogenesis remains. This hypothesis requires confirmation in large-scale future prospective trials.

Application Of Electronic Evidence As Extension Of Legal Civil Evidence Divorce Cases In Indonesia

Electronic evidence serves as a crucial component in civil trials, such as divorce cases, offering comprehensive proof to sway judges and ensure justice and legal certainty for involved parties. Nonetheless, disagreement persists regarding its classification, whether as supplementary or primary evidence, posing significant questions within formal and material law. This study employs normative juridical legal research, which scrutinizes theories, concepts, legal principles, and statutory regulations pertinent to the subject. Under Article 5(1) of the ITE Law, electronic evidence, including electronic information, documents, and their printouts, is recognized as valid legal evidence, extending the scope of admissible evidence in Indonesia. Formal requirements for electronic evidence, or digital evidence, need not be in written form; printouts are considered presumptive or preliminary evidence. However, material requirements stipulate that digital evidence must guarantee authenticity, integrity, and availability, often necessitating testimony from digital forensic experts. This dual nature of electronic evidence highlights its importance and complexity in contemporary legal proceedings, demanding a nuanced understanding and application within the framework of Indonesian law.

Comparison of World Health Organization and International Consensus Classification Guidelines for Myeloid Neoplasms Harboring TP53-Mutations Using an Independent International Cohort

BACKGROUND: Recently proposed World Health Organization (WHO, 5 th edition) and International Consensus Classification (ICC) recognized myeloid neoplasms (MN) harboring TP53-mutated ( TP53mut) as a separate entity. However, there are critical differences between the two classifications regarding allelic-status, variance allele frequency (VAF) cut-off and blast categories, that may lead to under- or overestimation of the risk. METHODS: We analyzed MN harboring TP53mut (VAF ≥2%, n=536) managed at Mayo Clinic (USA) and South Australia Health Network (Australia). ICC (Arber et al, Blood 2022) and WHO (Bluebook, Beta v2) definitions were used to stratify MN harboring TP53mut. RESULTS: Of 536 cases, 379 (71%) had myelodysplastic syndromes (MDS) (<20% blasts) and 157 (29%) had acute myeloid leukemia (AML). Using WHO, 160 (42%) of 379 were classified as MDS-bi TP53 as they harbored 2 TP53mut (n=115; 30%) or 1 TP53mut plus confirmed loss of heterozygosity (LOH) or copy neutral LOH (cnLOH) of TP53 locus (n=45; 12%). Sixty-two (16%) TP53mut MDS with VAF >49% were classified as presumptive MDS-bi TP53. Of the 157 cases with 1 TP53mut VAF ≤49%, 17 confirmed to have an intact wild-type TP53 copy and were classified as monoallelic. While 140 (89%) cases did not have copy number variation (CNV) analysis. We next evaluated the number of TP53mut cases classified differently by WHO and ICC. As WHO does not recognize TP53mut AML as a separate entity, 157 (29%) TP53mut AML were not classifiable. 46% (174/379) of the TP53mut MDS including 48 (30%), 12 (19%) and 79 (65%) of bi TP53, presumptive bi TP53 and monoallelic TP53mut MDS according to WHO were classified differently by ICC ( Figure 1A). Discordance between the two classifications were predominantly driven by: (i) The difference in VAF cut-off. Sixty patients (11%) with TP53mut VAF <10% were excluded from the ICC classification of TP53mut MN as it mandates TP53mut VAF cut-off ≥10%. 11 (18%) and 41 (68%) of these had bi TP53, monoallelic TP53mut MDS by WHO criteria while 8 (13%) had AML. Importantly, within the VAF <10% cohort, median overall survival (OS) of 2 TP53mut or 1 TP53mut with 17p13.1 (hereafter 17p) deletion or complex karyotype (CK, n=30) was significantly poor compared to 1 TP53mut VAF <10% (11.6 vs 32.4 months; P =0.002, Figure 1B), suggesting that ICC may underestimate the poor prognosis of multi-hit or multi-hit equivalent TP53mut MN with VAF <10%. (ii) The difference in bone marrow blast cut-off. The underlying assumption by WHO is that prognosis of bi TP53mut MDS is poor irrespective of blast percentage category (0-9% vs 10-19%). In contrast, ICC considers that TP53mut MDS/AML (blasts 10-19%) is associated with poor prognosis irrespective of TP53 allelic status. Median OS of TP53mut MDS with 10-19% blasts was significantly poor compared to blast 0-9% (6.4 vs 11.6 months, P <0.0001). Second, median OS of bi TP53mut was significantly poor than monoallelic TP53mut in MDS- blast 0-9% (10.1 vs 15.9 months; P =0.0001) but not in blasts 10-19% (6.8 vs 6.2 months; P =0.19). Hence, exclusion of monoallelic TP53mut MDS with blast 10-19% as TP53mut MN from the WHO classification may underestimate the poor prognosis. (iii) The difference in the definition of biallelic and multi-hit TP53 loss. 35 cases with 1 TP53mut VAF ≤49%, had 17p deletion but did not have CNV analysis to confirm the loss of TP53 locus and could not be classified further using WHO. ICC classified 18 (50%) of these cases as multi-hit. Median OS of 1 TP53mut VAF ≤49%, and 17p deletion on karyotype was significantly poor than 1 TP53mut (VAF ≤49%without 17p deletion on karyotype (6.4 vs 14.6 months, P =0.001). (iv) The difference in the definition of multi-hit equivalent. 32% (33/104) WHO defined monoallelic cases without available CNV data, were classified as multi-hit-equivalent by ICC as they harbored CK. However, WHO does not consider CK as presumptive evidence of bi TP53. Median OS of 1 TP53mut VAF ≤49% with CK was significantly poor compared to 1 TP53mut without CK (8.2 vs 26.9 months, P =0.0008). CONCLUSION: Our study provides evidence that poor prognosis of ‘multi-hit’ TP53 with VAF <10% is underestimated by ICC. On the other hand, poor prognosis of monoallelic TP53 MDS with 10-19% blasts as well as 1 TP53mut VAF ≤49% in the presence of CK is underestimated by WHO. These data suggest that both classifications can be further refined.

A Lesson from a Measles Outbreak among Healthcare Workers in a Single Hospital in South Korea: The Importance of Knowing the Prevalence of Susceptibility.

Despite the high vaccination coverage rate, in-hospital transmission of measles continues to occur in South Korea. We present a measles outbreak in which two healthcare workers (HCWs) with presumptive evidence of measles immunity were infected by a patient with typical measles at a single hospital in South Korea. This facilitated the evaluation of measles seroprevalence in all HCWs. In 2018, suspected patients and contacts exposed during a measles outbreak were investigated based on their medical histories and vaccination status. Cases were confirmed by the detection of measles-specific immunoglobulin M or RNA. After the measles outbreak in 2018, measles IgG testing was conducted on a total of 972 HCWs for point-prevalence, including those exposed to the measles. In addition, we have routinely performed measles IgG tests on newly employed HCWs within one week of their hire date since 2019. The measles vaccine was administered to HCWs who tested negative or equivocally negative for IgG antibodies. An index patient who returned from China with fever and rash was diagnosed with measles at a hospital in Korea. Two additional HCWs were revealed as measles cases: one was vaccinated with the two-dose measles-mumps-rubella (MMR) vaccine, and the other, who was born in 1967, was presumed to have immunity from natural infection in South Korea. All three patients harbored the same D8 genotype. No additional measles cases were identified among the 964 contacts of secondary patients. A total of 2310 HCWs, including those tested during the 2018 outbreak, underwent measles IgG tests. The average age at the time of the test was 32.6 years, and 74.3% were female. The overall seropositivity of measles was 88.9% (95% confidence interval, 87.5-90.1). Although the birth cohorts between 1985 and 1994 were presumed to have received the measles-rubella (MR) catch-up vaccination in 2001, 175 (89.3%) HCWs were born after 1985 among the 195 seronegative cases. Despite high population immunity, imported measles transmission occurred among HCWs with presumed immunity. This report underscores the importance of understanding the prevalence of measles susceptibility among newly employed HCWs. This is important for policymaking regarding hospital-wide vaccinations to prevent the spread of vaccine-preventable diseases.

Management of acquired bronchobiliary fistula: A case report

Bronchobiliary fistula (BBF) is an abnormal connection between the bronchial system and biliary tree. It is a rare condition that often manifests as bilioptysis. BBF has several causes; however infectious disease of the liver and lungs, mostly hydatid cysts, is the leading cause of BBF. For a conclusive diagnosis, imaging studies are useful and able to show the fistula tract, as we did by CT scan. The treatment of BBF is still a challenge for surgeons. In children, in the acute fulminating phase, an aggressive and rapid approach is essential to prevent respiratory tract damage. We present a case of a 17-year-old girl, who complained of bilioptysis, chest pain and loss of appetite for about nine months. Her past history revealed that she developed bilioptysis after laparotomy for excision of liver hydatid cyst 10 months ago. For which she underwent conservative and surgical treatment of bilioptysis, which all failed. After investigations, a bronchobiliary fistula was identified. A right thoracotomy was performed. After the release of adhesions and debridement of damaged tissues, the fistula tract was excised. The connection was sealed by a diaphragmatic muscle flap, which was successful in the outcome after 12 months of follow-up. BBF is a condition that requires strong presumptive evidence for diagnosis and a well-planned approach for management. Hence, each surgeon must carefully consider the optimal method for open surgery or conservative therapy after thoroughly evaluating the patient's profile and imaging. In children, a thoracic approach with a diaphragmatic flap is safe, easily available, and can easily divide the lung from the liver since that is its normal function.

PRESUMPTIVE DIAGNOSIS OF SPINA BIFIDA IN CANINE PATIENT

The aim of this report is to describe a presumptive diagnosis of spina bifida in a mixed breed dog, due to previous diagnostic inconsistencies. Spina bifida is an uncommon congenital anomaly characterized by poor bone formation due to incomplete closure or the absence of the dorsal arch of the vertebral structure during the process of embryogenesis. Animals with this condition may have difficulties in the locomotion process, which constantly threatens the quality and survival of those affected. Spina bifida can present itself in four different forms and to varying degrees. A 5-month-old mixed breed dog was seen at a veterinary clinic in Conselheiro Lafaiete/MG with difficulties in the locomotion process and previous diagnostic inconsistencies in other veterinary services. On physical examination, he had kyphosis in the thoracic region and decreased proprioceptive capacity in the hind limbs. After radiographs were taken, morphological thoracic alterations were observed in the segment between the T5 to T9 vertebrae, with duplicated spinous processes and a decrease in the dimensions of the intervertebral space. The radiographic examination suggested presumptive evidence of thoracic spina bifida due to the unavailability of the tutor to perform more sensitive exams such as tomography and magnetic resonance. Therefore, drugs for pain and neuropathic control such as gabapentin and pregabalin were prescribed, at different times, until new recommendations, which have shown therapeutic efficacy to the patient. Currently, the patient uses a wheelchair adapted for locomotion due to the loss of movement of the hind limbs, in addition to weekly physical therapy follow-up and acupuncture sessions.

Presumptive evidence and legal fiction as specific legal remedies of judicial economy in the civil proceedings

Presumptive evidence and legal fiction as specific legal remedies of judicial economy in the civil proceedings

Successful collaboration in online learning through skills and community building: a women in leadership MBA subject case study

Harasim’s Collaborativism and Garrison’s Community of Inquiry are underpinned by the notion that successful online peer-peer collaboration leads to deep learning and that online learners require scaffolded facilitator support to successfully collaborate. This support includes two actions: firstly, transitioning students from the roles of face-to-face learners to online learners so they know what to do and how to do it in a new learning environment and secondly, building a strong online community that sets the positive cognitive and behavioural building blocks that underpin successful collaboration. Collaborativism sees learners progressing through distinct discourse-focussed collaboration stages in order to achieve new, deep knowledge acquisition and Community of Inquiry proposes the convergence of Social Presence, Teaching Presence, and Cognitive Presence to achieve the same. Linking theory to practice, Salmon’s 5-Stage Model for Online Learning complements these frameworks by providing facilitators with a practical online learning model, with embedded learning activities, providing the tools to create a strong online learner community. These three theorists bring Social Constructivism to the online learning space. MBA661 Gendered Workplace Environments v1, is a higher education subject, placed at an Australian Qualifications Framework level 9 (AQF-9), and at a Master of Business Administration level 600 (MBA-600). It sits within a Women in Leadership specialisation stream. It is used here in an illustrative case study on how to successfully apply these theories and aligned model to achieve online Social Constructivism. The educational philosophy used in its syllabus design and facilitation was to put community building activities before content teaching so that technology and collaboration skills were developed in a supportive, scaffolded manner, better equipping students to then engage in effective, collaborative content learning. This case study provides presumptive evidence that placing community building activities before content teaching within weekly lesson plans results in strong student collaboration skills development that may contribute to higher student satisfaction levels with collaborative learning.

Comparison of myeloid neoplasms with nonclassic 3q26.2/MECOM versus classic inv(3)/t(3;3) rearrangements reveals diverse clinicopathologic features, genetic profiles, and molecular mechanisms of MECOM activation.

MECOM rearrangements are recurrent in myeloid neoplasms and associated with poor prognosis. However, only inv(3)(q21q26.2) and t(3;3)(q21;q26.2), the classic MECOM rearrangements resulting in RPN1-MECOM rearrangement with Mecom overexpression and GATA2 haploinsufficiency, define the distinct subtype of acute myeloid leukemia (AML), and serve as presumptive evidence for myelodysplastic syndrome based on the current World Health Organization classification. Myeloid neoplasms with nonclassic 3q26.2/MECOM rearrangements have been found to be clinically aggressive, but comparative analysis of clinicopathologic and genomic features is limited. We retrospectively studied cohorts of myeloid neoplasms with classic and nonclassic MECOM rearrangements. Cases with classic rearrangements consisted predominantly of AML, often with inv(3) or t(3;3) as the sole chromosome abnormality, whereas the group of nonclassic rearrangements included a variety of myeloid neoplasms, often with complex karyotype without TP53 mutations and similarly dismal overall survival. Immunohistochemistry revealed Mecom protein overexpression in both groups, but overexpression in cases with nonclassic rearrangements was mediated through a mechanism other than GATA2 distal enhancer involvement typical for classic rearrangement. Our results demonstrated that myeloid neoplasms with nonclassic 3q26.2/MECOM rearrangements encompass a diverse group of diseases with poor clinical outcome, overexpression of Mecom protein as a result of the nonclassic mechanism of MECOM activation.

PREVALENCE OF MEASLES IGG ANTIBODIES AMONG HEALTHCARE WORKERS IN BULGARIA

Background: Healthcare workers are at greater risk of acquiring measles than the general population. Transmission occurs from infected patients to staff and from infected staff to patients and colleagues. In inpatient and outpatient settings, susceptible patients suffering from other conditions, especially the elderly and severely ill patients in intensive care units are at a high risk of severe disease or death if infected with measles. The most effective preventive measure against measles is vaccination with two doses of a measles-containing vaccine. Aim: To perform a serological assessment of the presence of measles IgG antibodies among healthcare workers. Materials and Methods: The present study involves serological testing performed on samples from persons working in hospitals and Regional Health Inspectorates in the country. Screening started in connection with a reported measles outbreak in Bulgaria in 2019, and continued into early 2020. An indirect ELISA assay for the detection of specific measles IgG antibodies in serum samples was used. Results: The tested 152 healthcare workers were from 5 regions of the country, i.e. Sofia-capital (n=87), Burgas (n=6), Blagoevgrad (n=5), Dobrich (n=8) and Pazardzhik (n=46). Anti-measles IgG antibodies were detected in 85.5% of the participants (130/152). Negative results, indicating a possible lack of protective immunity against measles, were obtained primarily in samples from persons younger than 40 years of age. Conclusion: Screening to identify healthcare workers who lack presumptive evidence of protective immunity against measles should be reinforced, especially among younger healthcare workers, in order to minimize the risk of measles both among healthcare workers and among patients.

Evaluating tests for diagnosing COVID-19 in the absence of a reliable reference standard: pitfalls and potential solutions

Evaluating tests for diagnosing COVID-19 in the absence of a reliable reference standard: pitfalls and potential solutions

WS3.3. The Values of H-Reflex and Other Late Responses in Disease

It is relatively easy to record the H reflex from soleus, and many authorities still teach that it can be obtained only from this muscle. Inability to record the soleus H reflex has three possible causes: (i) poor technique; (ii) low central excitability; (iii) loss of afferent fibres due to, e.g., peripheral neuropathy or nerve root pathology. If the reason is (ii), all reflexes, in upper and lower limbs, will be difficult to elicit, and the reflex response should then become apparent during a steady voluntary contraction. A voluntary contraction not only potentiates the reflex but it also decreases the stimulus intensity needed for the reflex, ensures that the reflex involves the contracting muscle, and greatly reduces the attenuation of the response that occurs with higher stimulus rates. It reduces the latency of the reflex responses only slightly (<0.5 ms). During a steady voluntary contraction of the test muscle, H reflexes can be recorded for most limb muscles, and provide information about conduction across the most relevant spinal segments (e.g., C5/6, C6, C6/7, C8/T1, L3/4, L4/5 and S1). In routine diagnostic practice, I assess reflex conduction in perhaps 60% of patients because this provides insight into conduction in afferent and efferent axons over the entire peripheral nerve pathway. In diagnostic practice we focus on pathology that causes loss of reflex function. However, if you can record H reflexes at rest from muscles that normally have no H reflex unless they are contracting voluntarily, there is presumptive evidence of hyperreflexia. If there is EMG evidence of denervation in that muscle, this suggests UMN and LMN changes for a single muscle, and this is support for a diagnosis of motor neurone disease. F waves can provide complementary information about motor axons because the H reflex preferentially involves slowly conduction motor axons from small low-threshold motoneurones, but the F wave measures conduction in larger axons that are not discharged reflexly by the intense afferent volley produced by the supramaximal stimulus.

British Society for Haematology guidelines for the diagnosis and evaluation of prognosis of Adult Myelodysplastic Syndromes.

British Society for Haematology guidelines for the diagnosis and evaluation of prognosis of Adult Myelodysplastic Syndromes.

Clinical relevance of clonal hematopoiesis in persons aged ≥80 years

AbstractClonal hematopoiesis of indeterminate potential (CHIP) is associated with increased risk of cancers and inflammation-related diseases. This phenomenon becomes common in persons aged ≥80 years, in whom the implications of CHIP are not well defined. We performed a mutational screening in 1794 persons aged ≥80 years and investigated the relationships between CHIP and associated pathologies. Mutations were observed in one-third of persons aged ≥80 years and were associated with reduced survival. Mutations in JAK2 and splicing genes, multiple mutations (DNMT3A, TET2, and ASXL1 with additional genetic lesions), and variant allele frequency ≥0.096 had positive predictive value for myeloid neoplasms. Combining mutation profiles with abnormalities in red blood cell indices improved the ability of myeloid neoplasm prediction. On this basis, we defined a predictive model that identifies 3 risk groups with different probabilities of developing myeloid neoplasms. Mutations in DNMT3A, TET2, ASXL1, or JAK2 were associated with coronary heart disease and rheumatoid arthritis. Cytopenia was common in persons aged ≥80 years, with the underlying cause remaining unexplained in 30% of cases. Among individuals with unexplained cytopenia, the presence of highly specific mutation patterns was associated with myelodysplastic-like phenotype and a probability of survival comparable to that of myeloid neoplasms. Accordingly, 7.5% of subjects aged ≥80 years with cytopenia had presumptive evidence of myeloid neoplasm. In summary, specific mutational patterns define different risk of developing myeloid neoplasms vs inflammatory-associated diseases in persons aged ≥80 years. In individuals with unexplained cytopenia, mutational status may identify those subjects with presumptive evidence of myeloid neoplasms.

Nationwide epidemiological approach to identify associations between keratoconus and immune-mediated diseases

BackgroundThe aetiology of keratoconus (KC) remains poorly understood. KC has typically been described as a non-inflammatory disorder of the cornea. Nonetheless, there is increasing presumptive evidence for the role of...

Are Comorbid Disorders Associated with Changes in Gambling Activity? A Longitudinal Study of Younger and Older Subjects with DSM-IV Pathological Gambling.

This study investigates the association of comorbid disorders with gambling activity in a longitudinal follow-up study of younger and older adult subjects with DSM-IV pathological gambling (PG). The subjects included 57 younger adults with PG (≥ 18/ < 40years) and 48 older adults with PG (≥ 60years). Subjects were assessed at baseline and every 6months for a mean (SD) of 31.4 (13.1) months. Comorbidity was assessed using a modification of the Longitudinal Interval Follow-up Evaluation (LIFE). During follow-up, rates of problem severity were highest for anxiety disorders, mood disorders, and impulse control disorders. Among all subjects with PG, greater severity of depression or posttraumatic stress disorder was associated with increased gambling activity. In older subjects, greater severity of agoraphobia and social phobia were associated with lowered gambling activity. In younger subjects, greater severity of any substance use disorder, an alcohol use disorder, or compulsive computer use were associated with lowered gambling activity. The latter findings provide presumptive evidence for the substitute addiction hypothesis. We conclude that increased severity of several comorbid disorders could serve as triggers for increased gambling or predict lowered gambling activity. On the other hand, certain comorbid disorders could be triggered by increased gambling activity. Knowing these interrelationships is important to gaining a better understanding of PG and its clinical management.

A Cross-sectional Serological Study for Measles among Italian Medical Students in 2020

Background: Measles is an infectious disease and a major health concern worldwide. Among individuals with a higher risk of exposure to measles, there are the Health Care Workers (HCWs), who may transmit the virus to other people. According to the Italian National Plan for Immunization and Prevention, all HCWs should have presumptive evidence of immunity to measles (documented two doses of MMR vaccination) or serological evidence of protective antibodies. Aim: The study aims to evaluate the immunological status, the vaccine coverage, and the protective IgG antibody titre for measles in medical students of the teaching hospital PoliclinicoTor Vergata (PTV). Methods: IgG measles antibodies titre was evaluated in a sample of 461 medical students undergoing annual health surveillance visits from January 1st to May 31th, 2020. Results: 73.7% of medical students showed protective measles IgG antibody levels. The immunization rate was higher among subjects aged less than 25 years with respect to students aged over 25 years (77.4% vs. 66.4%; P &lt;0,001). Furthermore, average antibody titre showed a statistically significant association with the age group (124,2 AU/ml for the age group 18-25 and 133,2 AU/ml among subjects aged 25 or more; P&lt;0.001). Conclusion: Our study shows a non-protective measles IgG antibody titre, especially among the older students. Therefore, it is essential to evaluate the serological levels, to vaccinate those subjects whose antibody level is not adequate, and promote the vaccination even in the general population.

Congenital Inclusion Body Hemolytic Anemia Associated with Epilepsy and Disordered Pyridoxine Metabolism

AbstractDURING the preceding decade there has been great interest in the clinical importance of vitamin B6, especially as it relates to the nervous and hematopoietic systems.1-14 The purpose of this communication is to report an unusual case of congenital hemolytic anemia associated with a convulsive disorder in which there was presumptive evidence to suggest a defect in pyridoxine metabolism. The patient was originally reported by Lange and Akeroyd in 1958.15 This paper will document the concluding events in the evolution of this curious syndrome. Unfortunately, the sudden death of our young patient precluded a therapeutic trial with pyridoxine. Nevetheless, we believe that sufficient data were obstained to justify reporting this case in some detail.

Presumptive Evidence for ADAR1 A-to-I Deamination at WA-sites as the Mutagenic Genomic Driver in Hepatocellular and Related ADAR1-Hi Cancers

In hepatocellular cancer (HCC) there is an over expression of the RNA editing enzyme ADAR1. Further, the prominent genomic somatic mutation signature in HCC is almost exclusively focused on mutations at A:T base pairs where A-to-G mutations far exceed T-to-C mutations (when read on the non-transcribed strand). A clear mechanism for this extreme transcriptional strand biased mutation signature, putatively associated with over expression of ADAR1 deaminase, is yet to be explicitly demonstrated. The standard description of this strand bias has been nominally called “Transcription Coupled Damage” (TCD) to distinguish it from more conventional “Transcription Coupled Repair” (TCR). We show that the TCD description does not satisfy all features of the molecular evidence. The conventional view is that ADAR1 is thought to target adenosines at WA-sites for editing to inosine (I) in double stranded RNA stem-loop structures in transcripts. Here we show that the totality of the molecular and cellular data on these mutation signatures provides strong presumptive evidence for a clear role for ADAR1-mediated A-to-I deamination at WA-sites as the mutagenic driver in hepatocellular and possibly other related ADAR1-Hi cancers displaying biased mutation features at A:T base pairs.

Interbrain Synchrony in the Expectation of Cooperation Behavior: A Hyperscanning Study Using Functional Near-Infrared Spectroscopy.

Expectation of others’ cooperative behavior plays a core role in economic cooperation. However, the dynamic neural substrates of expectation of cooperation (hereafter EOC) are little understood. To fully understand EOC behavior in more natural social interactions, the present study employed functional near-infrared spectroscopy (fNIRS) hyperscanning to simultaneously measure pairs of participants’ brain activations in a modified prisoner’s dilemma game (PDG). The data analysis revealed the following results. Firstly, under the high incentive condition, team EOC behavior elicited higher interbrain synchrony (IBS) in the right inferior frontal gyrus (rIFG) than individual EOC behavior. Meanwhile, the IBS in the IFG could predict the relationship between empathy/agreeableness and EOC behavior, and this prediction role was modulated by social environmental cues. These results indicate the involvement of the human mirror neuron system (MNS) in the EOC behavior and the different neural substrates between team EOC and individual EOC, which also conform with theory that social behavior was affected by internal (i.e., empathy/agreeableness) and external factors (i.e., incentive). Secondly, female dyads exhibited a higher IBS value of cooperative expectation than male dyads in the team EOC than the individual EOC in the dorsal medial prefrontal cortex (DMPFC), while in the individual EOC stage, the coherence value of female dyads was significantly higher than that of male dyads under the low incentive reward condition in the rIFG. These sex effects thus provide presumptive evidence that females are more sensitive to environmental cues and also suggest that during economic social interaction, females’ EOC behavior depends on more social cognitive abilities. Overall, these results raise intriguing questions for future research on human cooperative behaviors.