bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous assessment of mitochondrial DNA copy number and nuclear epigenetic age towards predictive models of development and aging
Authors: Win Phyo W. , Nyugen Julia , Morin Amanda L. , Newcomb Charles E. , Singh Shiva M. , Gomaa Noha , Castellani Christina A.
Published: January 2024

Objective

Mitochondrial dysfunction and nuclear epigenetic alterations, two hallmarks of aging, are associated with aberrant development and complex disease risk. Here, we report a method for the simultaneous assessment of mitochondrial DNA copy number (mtDNA-CN) and DNA methylation age (DNAm age) from the same DNA extraction using quantitative polymerase chain reaction (qPCR) and array data, respectively.

Result

We present methods for the concurrent estimation of mtDNA-CN and DNAm age from the same DNA samples. This includes qPCR to estimate mtDNA-CN, representing the number of circular mitochondrial genomes in a cell, and DNA methylation microarray data to estimate the epigenetic age of an individual. Further, we provide a method for the combination of these metrics into a shared metric termed ‘mtEpiAge’. This approach provides a valuable tool for exploring the interplay between mitochondrial dysfunction and nuclear epigenetic alterations, and their associations with disease and aging.
Associations between genetically predicted plasma protein levels and Alzheimer’s disease risk: a study using genetic prediction models
Authors: Zhu Jingjing , Liu Shuai , Walker Keenan A. , Zhong Hua , Ghoneim Dalia H. , Zhang Zichen , Surendran Praveen , Fahle Sarah , Butterworth Adam , Alam Md Ashad , Deng Hong-Wen , Wu Chong , Wu Lang
Published: January 2024

Background

Specific peripheral proteins have been implicated to play an important role in the development of Alzheimer’s disease (AD). However, the roles of additional novel protein biomarkers in AD etiology remains elusive. The availability of large-scale AD GWAS and plasma proteomic data provide the resources needed for the identification of causally relevant circulating proteins that may serve as risk factors for AD and potential therapeutic targets.

Methods

We established and validated genetic prediction models for protein levels in plasma as instruments to investigate the associations between genetically predicted protein levels and AD risk. We studied 71,880 (proxy) cases and 383,378 (proxy) controls of European descent.

Results

We identified 69 proteins with genetically predicted concentrations showing associations with AD risk. The drugs almitrine and ciclopirox targeting ATP1A1 were suggested to have a potential for being repositioned for AD treatment.

Conclusions

Our study provides additional insights into the underlying mechanisms of AD and potential therapeutic strategies.
Superior mesenteric vein thrombosis due to COVID-19 vaccination: a case report
Authors: Suto Keita , Saito Akira , Mori Katsusuke , Yoshida Atsushi , Sata Naohiro
Published: January 2024

Background

The worldwide vaccination response to COVID-19 has been associated with rare thrombotic complications, including the case of postvaccination splanchnic venous thrombosis we report here.

Case presentation

An 80-year-old Japanese male with abdominal pain presented to our hospital six days after receiving a dose of the COVID-19 messenger ribonucleic acid vaccine. Abdominal computed tomography showed localized edema of the small intestine, increased density of the surrounding adipose tissue, and a thrombus in the superior mesenteric vein. Conservative inpatient treatment with unfractionated heparin relieved the thrombosis, and the patient is currently receiving oral apixaban as an outpatient.

Conclusion

Reported cases of thrombosis after COVID-19 vaccination typically have been associated with viral vector vaccines, with few reports of thrombosis induced by mRNA vaccines. The potential for venous thrombosis should be explored when patients present with abdominal pain soon after COVID-19 vaccination.
Biochemical characterization of a regiospecific flavonoid 3'-O-methyltransferase from orange
Authors: Park Hye Lin , Bhoo Seong Hee , Lee Sang-Won , Cho Man-Ho
Published: January 2024

Citrus plants have diverse methoxyflavonoids including, chrysoeriol, isosakuranetin, and nobiletin. In plants, O-methyltransferases (OMTs) participate in the methylation of a vast array of secondary metabolites, including flavonoids, phenylpropanoids, and alkaloids. To identify functional OMTs involved in the formation of methoxyflavonoids, orange (Citrus sinensis) OMT (CsOMT) genes were retrieved from the Citrus Genome Database. The phylogenetic relationships with functional OMTs suggested that three CsOMTs, CsOMT15, CsOMT16, and CsOMT30, are possible candidates for flavonoid OMTs (FOMTs). These CsOMTs were heterologously expressed in Escherichia coli, and their OMT activity was examined with flavonoid substrates. Of the examined CsOMTs, CsOMT16 catalyzed the regiospecific 3'-O-methylation of flavonoids to the respective 3'-methoxyflavonoids. A kinetic study demonstrated that CsOMT16 accepts diverse flavonoids as a substrate with a comparable preference. The flavonoids eriodictyol, luteolin, and quercetin were efficiently converted to homoeriodictyol, chrysoeriol, and isorhamnetin by CsOMT16-transformed E. coli cells, respectively. These findings suggest that CsOMT16 contributes to the methoxyflavonoid formation in orange and is applicable to the biotechnological production of 3'-methoxyflavonoids.
Impact of congenital uterine anomalies on reproductive outcomes of IVF/ICSI-embryo transfer: a retrospective study
Authors: Kang Jia , Qiao Jie
Published: January 2024

Objective

To study the impact of congenital uterine anomalies on reproductive outcomes after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)-embryo transfer (ET).

Methods

A retrospective study including a total of 865women with congenital uterine anomalies and 865 age and admission time matched controls who underwent the first IVF/ICSI-ET cycle between January 2010 and December 2019 was conducted. Women with uterine anomalies were classified into canalization defect (complete septate uterus and subseptate uterus) and unification defect (unicornuate uterus, bicornuate uterus, and didelphus uterus) according to the processes of abnormal embryological development. Control women were selected by age (± 1.0 year) and admission time (± 6 months) matched with a 1:1 ratio. The reproductive outcomes were compared between women with uterine anomalies and the controls. The primary outcome was live birth; secondary outcomes were clinical pregnancy, ectopic pregnancy, preterm delivery, and spontaneous pregnancy loss.

Results

Compared with women with a normal uterus, women with canalization defects were less likely to experience live birth [84/332 (25.3%) vs 128/332 (38.6%), RR: 0.647, 95% CI 0.513–0.815, P < 0.001]. They also had a lower clinical pregnancy rate [126/332 (38.0%) vs 206/332 (62.0%), RR: 0.829, 95% CI 0.690–0.997, P = 0.046] and experienced a higher first-trimester pregnancy loss rate [25/126 (19.8%) vs 11/206 (5.3%), RR: 2.716, 95% CI 1.393–5.295, P = 0.003]. Compared with women with a normal uterus, women with a unification defect were also less likely to experience live birth [132/533 (24.8%) vs 219/533 (41.1%), RR: 0.713, 95% CI 0.586–0.868, P = 0.001]. Women with a unification defect had lower clinical pregnancy rates [182/533 (34.1%) vs 263/533 (49.1%), RR: 0.813, 95% CI 0.695–0.952, P = 0.010] and increased first-trimester pregnancy loss [36/182 (19.8%) vs 20/263 (7.6%), RR: 3.288, 95% CI 1.776–6.085, P < 0.001]. While uterine anomaly seemed not increase the risk of preterm birth, ectopic pregnancy and second-trimester pregnancy loss.

Conclusions

Both canalization defects and unification defects were associated with lower fertility outcomes, including lower live birth rates, lower clinical pregnancy rates, and higher early miscarriage rates.
Identification of potential biomarkers and therapeutic targets related to post-traumatic stress disorder due to traumatic brain injury
Authors: Qi Peng , Huang Mengjie , Ren Xuewen , Zhai Yongzhi , Qiu Chen , Zhu Haiyan
Published: January 2024

Background

Post-traumatic stress disorder (PTSD), a disease state that has an unclear pathogenesis, imposes a substantial burden on individuals and society. Traumatic brain injury (TBI) is one of the most significant triggers of PTSD. Identifying biomarkers associated with TBI-related PTSD will help researchers to uncover the underlying mechanism that drives disease development. Furthermore, it remains to be confirmed whether different types of traumas share a common mechanism of action.

Methods

For this study, we screened the eligible data sets from the Gene Expression Omnibus (GEO) database, obtained differentially expressed genes (DEGs) through analysis, conducted functional enrichment analysis on the DEGs in order to understand their molecular mechanisms, constructed a PPI network, used various algorithms to obtain hub genes, and finally evaluated, validated, and analyzed the diagnostic performance of the hub genes.

Results

A total of 430 upregulated and 992 down-regulated differentially expressed genes were extracted from the TBI data set. A total of 1919 upregulated and 851 down-regulated differentially expressed genes were extracted from the PTSD data set. Functional enrichment analysis revealed that the differentially expressed genes had biological functions linked to molecular regulation, cell signaling transduction, cell metabolic regulation, and immune response. After constructing a PPI network and introducing algorithm analysis, the upregulated hub genes were identified as VNN1, SERPINB2, and ETFDH, and the down-regulated hub genes were identified as FLT3LG, DYRK1A, DCN, and FKBP8. In addition, by comparing the data with patients with other types of trauma, it was revealed that PTSD showed different molecular processes that are under the influence of different trauma characteristics and responses.

Conclusions

By exploring the role of different types of traumas during the pathogenesis of PTSD, its possible molecular mechanisms have been revealed, providing vital information for understanding the complex pathways associated with TBI-related PTSD. The data in this study has important implications for the design and development of new diagnostic and therapeutic methods needed to treat and manage PTSD.
Do risk factors differentiate DSM-5 and drive for thinness severity groups for anorexia nervosa?
Authors: Dang An Binh , Kiropoulos Litza , Anderluh Marija , Collier David , Fernandez-Aranda Fernando , Karwautz Andreas , Treasure Janet , Wagner Gudrun , Krug Isabel
Published: January 2024

Background

The current study examined whether risk factors for anorexia nervosa (AN) were related to different levels of severity based on (a) the DSM-5/body mass index (BMI) and (b) drive for thinness (DT) severity ratings.

Methods

The sample comprised 153 pairs of individuals with a lifetime diagnosis AN per DSM-IV criteria and their non-ED sisters (N = 306, mean age = 26.53; mean current BMI = 20.42 kg/m2). The Oxford risk factor interview was used to establish AN-related risk factors. Individuals were categorised into the DSM-5 severity groups based on their lowest BMI, while the DT subscale from the eating disorder inventory-2 was used to classify individuals with AN into low and high DT groups.

Results

Multinominal regression models showed similar risk factors (e.g., perfectionism, having a history of being teased about weight and shape) contributed to the development of AN using the DSM-5 and DT severity ratings. Follow-up analyses across the severity groups for both indices revealed that only childhood perfectionism was found to be more common in the extreme severe DSM-5 BMI severity group compared to the severe DSM-5 group.

Conclusion

Overall, this study found little evidence for AN risk factors being related to the DSM-5 and DT severity ratings. However, given the novelty of this study, replication of the current results is warranted.
Utilization of microalgae for agricultural runoff remediation and sustainable biofuel production through an integrated biorefinery approach
Authors: Rana Qurrat ul ain , Latif Saira , Perveen Saleha , Haq Abdul , Ali Sidra , Irfan Muhammad , Gauttam Rahul , Shah Tawaf Ali , Dawoud Turki M. , Wondmie Gezahign Fentahun , Bourhia Mohammed , Badshah Malik
Published: January 2024

Generally wastewater such agricultural runoff is considered a nuisance; however, it could be harnessed as a potential source of nutrients like nitrates and phosphates in integrated biorefinery context. In the current study, microalgae Chlorella sp. S5 was used for bioremediation of agricultural runoff and the leftover algal biomass was used as a potential source for production of biofuels in an integrated biorefinery context. The microalgae Chlorella sp. S5 was cultivated on Blue Green (BG 11) medium and a comprehensive optimization of different parameters including phosphates, nitrates, and pH was carried out to acquire maximum algal biomass enriched with high lipids content. Dry biomass was quantified using the solvent extraction technique, while the identification of nitrates and phosphates in agricultural runoff was carried out using commercial kits. The algal extracted lipids (oils) were employed in enzymatic trans-esterification for biodiesel production using whole-cell biomass of Bacillus subtilis Q4 MZ841642. The resultant fatty acid methyl esters (FAMEs) were analyzed using Fourier transform infrared (FTIR) spectroscopy and gas chromatography coupled with mass spectrometry (GC–MS). Subsequently, both the intact algal biomass and its lipid-depleted algal biomass were used for biogas production within a batch anaerobic digestion setup. Interestingly, Chlorella sp. S5 demonstrated a substantial reduction of 95% in nitrate and 91% in phosphate from agricultural runoff. The biodiesel derived from algal biomass exhibited a noteworthy total FAME content of 98.2%, meeting the quality standards set by American Society for Testing and Materials (ASTM) and European union (EU) standards. Furthermore, the biomethane yields obtained from whole biomass and lipid-depleted biomass were 330.34 NmL/g VSadded and 364.34 NmL/g VSadded, respectively. In conclusion, the findings underscore the potent utility of Chlorella sp. S5 as a multi-faceted resource, proficiently employed in a sequential cascade for treating agricultural runoff, producing biodiesel, and generating biogas within the integrated biorefinery concept.

Graphical Abstract
Daily yogurt consumption does not affect bone turnover markers in men and postmenopausal women of Caribbean Latino descent: a randomized controlled trial
Authors: McGrail Lindsay , Vargas-Robles Daniela , Correa Mayra Rojas , Merrill Lisa C. , Noel Sabrina E. , Velez Martha , Maldonado-Contreras Ana , Mangano Kelsey M.
Published: January 2024

Background

Caribbean Latino adults are at high risk for osteoporosis yet remain underrepresented in bone research. This increased risk is attributed to genetics, diet, and lifestyle known to drive inflammation and microbial dysbiosis.

Objective

The primary objective of this study was to determine whether consuming 5 oz of yogurt daily for 8wks improves bone turnover markers (BTMs) among Caribbean Latino adults > 50 years; and secondarily to determine the impact on the gut microbiota and markers of intestinal integrity and inflammation.

Methods

Following a 4wk baseline period, participants were randomized to an 8wk whole fat yogurt intervention (n = 10) daily, containing onlyStreptococcus thermophilusandLactobacillus bulgaricus,or to an untreated control group that did not consume yogurt (n = 10). Blood and stool samples collected at week-0 and week-8 were used to assess BTMs, inflammation, intestinal integrity biomarkers, and gut microbiota composition, short chain fatty acids (SCFAs), respectively. Data were evaluated for normality and statistical analyses were performed.

Results

Participants were 55% women, with a mean age of 70 ± 9 years, BMI 30 ± 6 kg/m2, and serum C-reactive protein 4.8 ± 3.6 mg/L, indicating chronic low-grade inflammation. Following 8wks of yogurt intake, absolute change in BTMs did not differ significantly between groups (P = 0.06–0.78). Secondarily, absolute change in markers of inflammation, intestinal integrity, and fecal SCFAs did not differ significantly between groups (Prange 0.13–1.00). Yogurt intake for 8wks was significantly associated with microbial compositional changes of rare taxa (P = 0.048); however, no significant alpha diversity changes were observed.

Conclusions

In this study, daily yogurt did not improve BTMs, inflammation, intestinal integrity, nor SCFAs. However, yogurt did influence beta diversity, or the abundance of rare taxa within the gut microbiota of the yogurt group, compared to controls. Additional research to identify dietary approaches to reduce osteoporosis risk among Caribbean Latino adults is needed.

Trial registration

This study is registered to ClinicalTrials.gov, NCT05350579 (28/04/2022).
Describing skin health and disease in urban-living Aboriginal children: co-design, development and feasibility testing of the Koolungar Moorditj Healthy Skin pilot project
Authors: Ricciardo Bernadette M. , Kessaris Heather-Lynn , Nannup Noel , Tilbrook Dale , Farrant Brad , Michie Carol , Hansen Lorraine , Douglas Richelle , Walton Jacinta , Poore Ainslie , Whelan Alexandra , Barnett Timothy C. , Kumarasinghe Prasad S. , Carapetis Jonathan R. , Bowen Asha C.
Published: January 2024

Background

Indigenous children in colonised nations experience high rates of health disparities linked to historical trauma resulting from displacement and dispossession, as well as ongoing systemic racism. Skin infections and their complications are one such health inequity, with the highest global burden described in remote-living Australian Aboriginal and/or Torres Strait Islander (hereafter respectfully referred to as Aboriginal) children. Yet despite increasing urbanisation, little is known about the skin infection burden for urban-living Aboriginal children. More knowledge is needed to inform service provision, treatment guidelines and community-wide healthy skin strategies. In this pilot study, we aimed to test the feasibility and design of larger multi-site observational studies, provide initial descriptions of skin disease frequency and generate preliminary hypotheses of association.

Methods

This project has been co-designed with local (Noongar) Elders to provide an Australian-first description of skin health and disease in urban-living Aboriginal children. In collaboration with an urban Aboriginal Community Controlled Health Organisation (Derbarl Yerrigan Health Service), we conducted a week-long cross-sectional observational cohort study of Aboriginal children (0–18 years) recruited from the waiting room. Participants completed a questionnaire, skin examination, clinical photos, and swabs and received appropriate treatment. We assessed the feasibility and impact of the pilot study.

Results

From 4 to 8 October 2021, we recruited 84 Aboriginal children of whom 80 (95%) were urban-living. With a trusted Aboriginal Health Practitioner leading recruitment, most parents (or caregivers) who were approached consented to participate. Among urban-living children, over half (45/80, 56%) of parents described a current concern with their child’s skin, hair and/or nails; and one-third (26/80, 33%) reported current itchy skin. Using a research-service model, 27% (21/79) of examined urban-living participants received opportunistic same-day treatment and 18% (14/79) were referred for later review.

Conclusions

This co-designed pilot study to understand skin health in urban-living Aboriginal children was feasible and acceptable, with high study participation and subsequent engagement in clinical care observed. Co-design and the strong involvement of Aboriginal people to lead and deliver the project was crucial. The successful pilot has informed larger, multi-site observational studies to more accurately answer questions of disease burden and inform the development of healthy skin messages for urban-living Aboriginal children.
Home-based cognitive bias modification training for reducing maladaptive fear in patients with suspected acute coronary syndrome: a pilot randomized clinical trial
Authors: Lopez-Veneros David , Cumella Robin , Kronish Ian M. , Lazarov Amit , Birk Jeffrey L.
Published: January 2024

Background

Patients evaluated in an emergency department for suspected acute coronary syndromes (ACS; e.g., myocardial infarction) often experience a lingering fear of recurrence, which may adversely affect their mental health and adherence to recommended health behaviors. Cognitive bias modification training (CBMT) is an acceptable, easy-to-use intervention that reduces fear of recurrence in cancer patients, and reduces fear and anxiety in other populations, providing an alternative to psychotherapy or counseling-based approaches. Feasibility testing is needed to assess whether a cardiac-related version of CBMT is acceptable to patients with elevated threat perceptions related to their suspected ACS.

Methods

We developed a tablet-based CBMT intervention tailored to reduce cardiac-related fear of recurrence. In this double-blinded feasibility trial, patients with elevated threat perceptions related to a recent suspected ACS were randomized either to a 4-week, 8-session, tablet-delivered intervention (CBMT) group or to a sham attention control group. Feasibility outcomes included the proportion of eligible patients who enrolled, drop-out rate, intervention compliance rate, acceptability/pleasantness and usability ratings, and task engagement (i.e., accuracy, response time).

Results

Of 49 eligible patients with suspected ACS and elevated threat perceptions recruited from NewYork-Presbyterian Hospital, over half (53.1%) enrolled after receiving a description of study procedures. Of the 26 randomized patients (mean age 59.15 years, 50% women), 2 patients (7.7%) dropped out. Additionally, 4 (15.4%) enrolled patients were not able to complete the tablet tasks, either due to difficulties with the technology or an inability to process the visually presented linguistic information at a sufficient speed. Still, among patients who returned the tablets (19 returned/20 received; 95%), most completed all assigned tablet tasks (intervention or control; 10/19; 52.6%), reporting that the tablets were easy to use and that the tasks were pleasant to complete.

Conclusion

Current findings suggest that cardiac-related CBMT is a promising and generally acceptable intervention for suspected ACS patients with cardiac-related threat perceptions which are akin to fear of recurrence. Nevertheless, challenges related to tablet usage indicate that the intervention user-experience should be further refined to optimize usability.

Trial registration

Registered at ClinicalTrials.gov on 2/25/2019; NCT03853213. Registered with the Open Science Framework on 11/20/2017; https://osf.io/k7g8c/.
Sodium-glucose co-transporter-2 inhibitors in patients treated with immune checkpoint inhibitors
Authors: Perelman Moran Gvili , Brzezinski Rafael Y. , Waissengrin Barliz , Leshem Yasmin , Bainhoren Or , Rubinstein Tammi Arbel , Perelman Maxim , Rozenbaum Zach , Havakuk Ofer , Topilsky Yan , Banai Shmuel , Wolf Ido , Laufer-Perl Michal
Published: January 2024

Background

Immune checkpoint inhibitors (ICIs) have revolutionized the prognosis of cancer. Diabetes mellitus (DM) has been shown to have a negative effect on patients treated with ICIs. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are effective antidiabetic therapies associated with reduced all-cause mortality and cardiovascular (CV) outcomes.

Objective

To evaluate the prognostic value of SGLT2i on all-cause mortality and cardiotoxicity among patients treated with ICIs.

Methods

We performed a retrospective analysis of patients diagnosed with cancer and type 2 DM (DM2) and treated with ICIs at our center. Patients were divided into two groups according to baseline treatment with or without SGLT2i. The primary endpoint was all-cause mortality and the secondary endpoint was MACE, including myocarditis, acute coronary syndrome, heart failure, and arrhythmia.

Results

The cohort included 119 patients, with 24 (20%) patients assigned to the SGLT2i group. Both groups exhibited a comparable prevalence of cardiac risk factors, although the SGLT2i group displayed a higher incidence of ischemic heart disease. Over a median follow-up of 28 months, 61 (51%) patients died, with a significantly lower all-cause mortality rate in the SGLT2i group (21% vs. 59%, p = 0.002). While there were no significant differences in MACE, we observed zero cases of myocarditis and atrial fibrillation in the SGLT2i, compared to 2 and 6 cases in the non-SGLT2i group.

Conclusions

SGLT2i therapy was associated with a lower all-cause mortality rate in patients diagnosed with cancer and DM2 and treated with ICIs. Further studies are needed to understand the mechanism and evaluate its benefit on cardiotoxicity.

Graphical Abstract
Ulnar nerve involvement at the wrist in idiopathic mild to moderate carpal tunnel syndrome: electrophysiological and ultrasonographic study
Authors: Elwakil Walaa , Sultan Hussein Elmoghazy , Hassan Marwa , Elshafei Mohamed , Hammad Esraa
Published: January 2024

Background

Carpal tunnel syndrome (CTS) is a common entrapment neuropathy. It is clinically presented by nocturnal pain, paresthesia, and weakness in the distribution of the median nerve. However, extra-median symptoms may develop in some patients, particularly those with mild to moderate CTS. This raised the assumption of possible concomitant ulnar nerve entrapment at the wrist, or Guyon's canal syndrome (GCS). The aim of this study is to evaluate functional and structural changes that may take place in the ulnar nerve at the wrist in those patients.

Methods

This is a retrospective case–control study that included forty patients with mild to moderate CTS and 40 matched subjects as a control group. Electrophysiological evaluation was done for all the participants in addition to measuring median and ulnar nerves sonographic parameters in the form of median cross-sectional area (m-CSA) at the level of pisiform bone, median flattening ratio (m-FR), median swelling ratio (m-SR), the difference between m-CSA at the inlet of the carpal tunnel and m-CSA at the distal third of the pronator quadratus (Δ m-CSA), as well as the ulnar cross-sectional area (u-CSA) at the same level.

Results

The u-CSA was larger in the patients relative to the control (5.23 ± 1.21 mm2 versus 3.28 ± 0.64 mm2). It did not correlate with m-CSA. However, a statistically significant correlation was demonstrated between u-CSA and median motor conduction parameters (P ≤ 0.001).

Conclusion

Although patients with mild to moderate idiopathic CTS may have normal electrophysiological parameters of the ulnar nerve, ultrasonographic evaluation is valuable to detect early ulnar nerve structural changes, which appear to be likely due to concomitant distal ulnar nerve entrapment at the Guyon’s canal, which may contribute to the development of extra-median symptoms in those patients.
Evaluating GPT-4-based ChatGPT's clinical potential on the NEJM quiz
Authors: Ueda Daiju , Walston Shannon L. , Matsumoto Toshimasa , Deguchi Ryo , Tatekawa Hiroyuki , Miki Yukio
Published: January 2024

Background

GPT-4-based ChatGPT demonstrates significant potential in various industries; however, its potential clinical applications remain largely unexplored.

Methods

We employed the New England Journal of Medicine (NEJM) quiz “Image Challenge” from October 2021 to March 2023 to assess ChatGPT's clinical capabilities. The quiz, designed for healthcare professionals, tests the ability to analyze clinical scenarios and make appropriate decisions. We evaluated ChatGPT's performance on the NEJM quiz, analyzing its accuracy rate by questioning type and specialty after excluding quizzes which were impossible to answer without images. ChatGPT was first asked to answer without the five multiple-choice options, and then after being given the options.

Results

ChatGPT achieved an 87% (54/62) accuracy without choices and a 97% (60/62) accuracy with choices, after excluding 16 image-based quizzes. Upon analyzing performance by quiz type, ChatGPT excelled in the Diagnosis category, attaining 89% (49/55) accuracy without choices and 98% (54/55) with choices. Although other categories featured fewer cases, ChatGPT's performance remained consistent. It demonstrated strong performance across the majority of medical specialties; however, Genetics had the lowest accuracy at 67% (2/3).

Conclusion

ChatGPT demonstrates potential for diagnostic applications, suggesting its usefulness in supporting healthcare professionals in making differential diagnoses and enhancing AI-driven healthcare.
Surveillance and characterization of avian-origin H3N2 canine influenza viruses in 2021 in China
Authors: Chen Mingyue , Wang Rui , Pei Ying , Zhang Ting , Lyu Yanli , McLaughlin Jonathan , Vemaraju Sai Subramanya Manasa , Wang Zhen , Sun Yipeng , Zhang Ming
Published: January 2024

Avian-origin H3N2 canine influenza virus (CIV) is one of the most prevalent influenza virus subtypes in dogs worldwide. Previous studies have shown that during the evolution of H3N2 CIV in dogs, its adaptability in mammals increased gradually, suggesting that dogs can serve as a potential intermediate host for cross-species transmission of the avian influenza virus. In this study, we report results from the surveillance and characterization of H3N2 CIVs isolated from animal hospitals and kennels in 2021 in China. We characterized the CIVs’ genetic and antigenic variation, receptor-binding specificity, and virulence in mice. The hemagglutinin (HA) phylogenetic result showed that these H3N2 CIVs belonged to Clade 5.1, a clade formed after 2019. Compared to the 2016–2019 strains in China, the 2021 H3N2 CIVs had similar antigenicity and receptor-binding specificity. The pathogenicity in mice was significantly reduced after infection with two 2021 strains, but the replication capacity was similar, suggesting that a virus-host balance might have been established. This report emphasizes the importance of close surveillance and monitoring of H3N2 CIVs in dogs to prevent the emergence of novel influenza viruses with public health threats.
Comparison of coercive practices in worldwide mental healthcare: overcoming difficulties resulting from variations in monitoring strategies
Authors: Savage Martha K. , Lepping Peter , Newton-Howes Giles , Arnold Richard , Staggs Vincent S. , Kisely Steven , Hasegawa Toshio , Reid Keith S. , Noorthoorn Eric O.
Published: January 2024

Background

Coercive or restrictive practices such as compulsory admission, involuntary medication, seclusion and restraint impinge on individual autonomy. International consensus mandates reduction or elimination of restrictive practices in mental healthcare. To achieve this requires knowledge of the extent of these practices.

Aims

We determined rates of coercive practices and compared them across countries.

Method

We identified nine country- or region-wide data-sets of rates and durations of restrictive practices in Australia, England, Germany, Ireland, Japan, New Zealand, The Netherlands, the USA and Wales. We compared the data-sets with each other and with mental healthcare indicators in World Health Organization and Organisation for Economic Cooperation and Development reports.

Results

The types and definitions of reported coercive practices varied considerably. Reported rates were highly variable, poorly reported and tracked using a diverse array of measures. However, we were able to combine duration measures to examine numbers of restrictive practices per year per 100 000 population for each country. The rates and durations of seclusion and restraint differed by factors of more than 100 between countries, with Japan showing a particularly high number of restraints.

Conclusions

We recommend a common set of international measures, so that finer comparisons within and between countries can be made, and monitoring of trends to see whether alternatives to restraint are successful. These measurements should include information about the total numbers, durations and rates of coercive measures. We urge the World Health Organization to include these measures in their Mental Health Atlas.
Oncofertility and Pregnancy in Adolescent and Young Adult Cancers: Physicians' Knowledge and Preferences in India
Authors: Mailankody Sharada , Bajpai Jyoti , Arora Puneet R. , Sreedharan Rinoy , Chitalkar Prakash , Kurkure Purna , Malhotra Hemant , Parikh Firuza R. , Gupta Sudeep , Banavali Shripad D.
Published: January 2024

PURPOSE

The treatment outcomes of adolescent and young adult (AYA) cancers have improved with advanced oncology care. Hence, fertility preservation (FP) and post-therapy pregnancies (PTPs) become vital issues.

MATERIALS AND METHODS

An online survey link with 17 questions regarding oncofertility and PTPs was circulated among oncologists to assess the knowledge, understand the oncofertility care patterns, and seek suggestions to improve oncofertility services.

RESULTS

The median age of 179 respondents, predominantly medical oncologists (68.7%), was 37 years (IQR, 10; range, 29-74), working in academic centers (39%) having a median experience of 4 years (IQR, 4; range, 1-42); 23 (12.8%) had dedicated AYA cancer units. Although a quarter (19%-24%) of respondents discussed fertility issues in >90% of AYA patients with cancer, only a tenth (8%-11%) refer >90% for FP, with significantly higher ( P < .05) discussions and referrals in males and by more experienced oncologists ( P < .05). Forty-six (25.6%) were not well versed with international guidelines for FP. Most (122, 68.1%) oncologists knew about the referral path for semen cryopreservation; however, only 46% were knowledgeable about additional complex procedures. One hundred and ten (61.5%) oncologists never or rarely altered the systemic treatment for FP. Prominent barriers to FP were ignorance, lack of collaboration, and fear of delaying cancer treatment. Lead thrust areas identified to improve FP practices are education, and enhanced and affordable access to FP facilities. Seventy-four (41.3%) respondents knew about international guidelines for PTPs; however, only half (20%) of them often monitored fertility outcomes in survivors. Oncologists have conflicting opinions and uncertainties regarding pregnancy safety, assisted reproductive techniques, breastfeeding, and pregnancy outcomes among survivors.

CONCLUSION

Oncologists are uncertain about the guidelines, FP practices, referral pathways, and PTPs. Multipronged approaches to improve awareness and provision for affordable oncofertility facilities are needed to enhance AYA cancer outcomes in India, which will be applicable to other low- and middle-income countries too.
Randomized Trial of a Volunteer-Led Symptom Assessment Intervention on Documentation, Patient-Reported Outcomes, and Health Care Use Among Veterans With Lung Cancer
Authors: Banks LaKedia Charman , Kapphahn Kris , Das Millie , Patel Manali I.
Published: January 2024

PURPOSE

Identification and documentation of Veterans' symptoms are crucial for optimal lung cancer care delivery. The objective of this study was to determine whether a volunteer-led proactive telephone symptom assessment intervention could improve comprehensive symptom documentation.

METHODS

Veterans with lung cancer were randomly assigned to usual care (control group) or usual care with proactive symptom assessment in which a peer volunteer made weekly phone calls to assess patient symptoms under nurse practitioner supervision. The primary outcome was oncologist documentation of symptoms in the electronic health record at all clinical visits within 6 months after enrollment. Secondary outcomes included patient satisfaction with decision, patient activation, health-related quality of life (HRQOL), and symptom burden, measured at baseline, and 3, 6, and 9 months after enrollment, and acute care use within 9 months after enrollment.

RESULTS

Among 60 Veterans randomly assigned, median (range) age was 70.2 (50-86) years; 57 (95.0%) were male. More intervention participants had oncologist documentation of symptoms than control group participants (24 [77.4%] v seven [24.1%], respectively; odds ratio, 16.46 [95% CI, 4.58 to 59.16]). Intervention group participants had greater improvements over time in HRQOL (expected mean difference, 25.3 [95% CI, 15.00 to 35.70]) and patient activation (expected mean difference, 13.6 [95% CI, 3.79 to 23.39]), lower symptom burden (expected mean difference, –6.39 [95% CI, –15.21 to –2.46]), lower rates of emergency room visits (incidence rate ratio, 0.48 [95% CI, 0.30 to 0.75]), and hospitalizations (incidence rate ratio, 0.47 [95% CI, 0.28 to 0.77]) than control group participants.

CONCLUSION

This symptom assessment intervention is an effective strategy for Veterans with lung cancer.
Somatic Versus Germline: A Case Series of Three Children With ATM-Mutated Medulloblastoma
Authors: Tam Lydia T. , Cole Bonnie , Stasi Shannon M. , Paulson Vera A. , Wright Jason N. , Hoeppner Corrine , Holtzclaw Susan , Crotty Erin E. , Ellenbogen Richard G. , Lee Amy , Ermoian Ralph P. , Lockwood Christina M. , Leary Sarah E.S. , Ronsley Rebecca
Published: January 2024

Somatic versus Germline—A Case Series of Three Children with ATM- mutated Medulloblastoma
Thyroiditis After Parathyroidectomy
Authors: Kwayess Rola , Cooper David S , Fuleihan Ghada El-Hajj
Published: January 2024

Various clinical manifestations of thyroiditis after parathyroidectomy have been reported in the literature, ranging from mild symptoms to tachyarrhythmias and myocardial infarction. We report 2 cases of post-parathyroidectomy thyroiditis. Both patients had primary hyperparathyroidism and underwent parathyroidectomy for a solitary parathyroid adenoma. They subsequently developed symptoms of hyperthyroidism, including palpitations and heat intolerance. Laboratory investigations demonstrated a suppressed TSH level with elevated free T4 levels and low uptake on thyroid radioiodine scan, confirming the diagnosis of thyroiditis. The patients were managed conservatively, and their symptoms gradually resolved with normalization of thyroid hormone levels. A review of 27 cases reported to date reveals that this condition is mostly attributed to manipulation of the thyroid during parathyroid surgery. It occurs more frequently in patients who undergo 4-gland parathyroidectomy for secondary or tertiary hyperthyroidism and is self-limited within a few weeks. The case reports highlight the importance of recognizing thyroiditis as a potentially underrecognized complication of parathyroid surgery. Further research is warranted to better understand the underlying pathophysiology and to establish potential risk factors for its development post-parathyroidectomy.
The Development of Skull Base Surgery as a Discipline: Remembrances of Dr Jon H. Robertson
Authors: Parikh Kara A. , Khan Nickalus , Sorenson Jeffrey M. , Gienapp Andrew J. , Robertson Jon H. , Michael L. Madison
Published: January 2024

Skull base surgery is a young surgical subspecialty currently led by its second generation of surgeons. At present, there is no literature that narrates the connection of the present to the past. An extended interview was held with Dr Jon H. Robertson, who helped establish the subspecialty in Memphis, TN, to aid in identifying and connecting sentinel events and key figures in the development of the discipline. The field drastically evolved during his era of practice (1975-present), with the advent of advanced imaging and technology, as well as the emergence of multidisciplinary skull base surgical teams. The intersection of the careers of Jon H. Robertson, James T. Robertson, Gale Gardner, Edwin Cocke, John Shea, Jr., and Jerrall Crook in Memphis catalyzed the standardization of a multidisciplinary approach to cranial base pathology. We report the findings of Dr Jon H. Robertson's extended interview, told against the backdrop of the history of the subspecialty. The story of the development of skull base surgery is told from the unique perspective of one who lived and shaped a pivotal segment in this historical timeline.
Control of successive unequal cell divisions by neural cell fate regulators determines embryonic neuroblast cell size
Authors: Mullan Thomas W. , Felton Terry , Tam Janis , Kasem Osama , Yeung Tim J. , Memar Nadin , Schnabel Ralf , Poole Richard J.
Published: January 2024

Asymmetric cell divisions often generate daughter cells of unequal size in addition to different fates. In some contexts, daughter cell size asymmetry is thought to be a key input to specific binary cell fate decisions. An alternative possibility is that unequal division is a mechanism by which a variety of cells of different sizes are generated during embryonic development. We show here that two unequal cell divisions precede neuroblast formation in the C lineage of Caenorhabditis elegans. The equalisation of these divisions in a pig-1/MELK mutant background has little effect on neuroblast specification. Instead, we demonstrate that let-19/MDT13 is a regulator of the proneural basic helix-loop-helix transcription factor hlh-14/ASCL1 and find that both are required to concomitantly regulate the acquisition of neuroblast identity and neuroblast cell size. Thus, embryonic neuroblast cell size in this lineage is progressively regulated in parallel with identity by key neural cell fate regulators. We propose that key cell fate determinants have a previously unappreciated function in regulating unequal cleavage, and therefore cell size, of the progenitor cells whose daughter cell fates they then go on to specify.
Assembly, dynamics and remodeling of epithelial cell junctions throughout development
Authors: Mira-Osuna Marta , Borgne Roland Le
Published: January 2024

Cell junctions play key roles in epithelial integrity. During development, when epithelia undergo extensive morphogenesis, these junctions must be remodeled in order to maintain mechanochemical barriers and ensure the cohesion of the tissue. In this Review, we present a comprehensive and integrated description of junctional remodeling mechanisms in epithelial cells during development, from embryonic to adult epithelia. We largely focus on Drosophila, as quantitative analyses in this organism have provided a detailed characterization of the molecular mechanisms governing cell topologies, and discuss the conservation of these mechanisms across metazoans. We consider how changes at the molecular level translate to tissue-scale irreversible deformations, exploring the composition and assembly of cellular interfaces to unveil how junctions are remodeled to preserve tissue homeostasis during cell division, intercalation, invagination, ingression and extrusion.
Mitochondrial function and sexual selection: can physiology resolve the ‘lek paradox’?
Authors: Crino Ondi L. , Head Megan L. , Jennions Michael D. , Noble Daniel W. A.
Published: January 2024

Across many taxa, males use elaborate ornaments or complex displays to attract potential mates. Such sexually selected traits are thought to signal important aspects of male ‘quality’. Female mating preferences based on sexual traits are thought to have evolved because choosy females gain direct benefits that enhance their lifetime reproductive success (e.g. greater access to food) and/or indirect benefits because high-quality males contribute genes that increase offspring fitness. However, it is difficult to explain the persistence of female preferences when males only provide genetic benefits, because female preferences should erode the heritable genetic variation in fitness that sexually selected traits signal. This ‘paradox of the lek’ has puzzled evolutionary biologists for decades, and inspired many hypotheses to explain how heritable variation in sexually selected traits is maintained. Here, we discuss how factors that affect mitochondrial function can maintain variation in sexually selected traits despite strong female preferences. We discuss how mitochondrial function can influence the expression of sexually selected traits, and we describe empirical studies that link the expression of sexually selected traits to mitochondrial function. We explain how mothers can affect mitochondrial function in their offspring by (a) influencing their developmental environment through maternal effects and (b) choosing a mate to increase the compatibility of mitochondrial and nuclear genes (i.e. the ‘mitonuclear compatibility model of sexual selection’). Finally, we discuss how incorporating mitochondrial function into models of sexual selection might help to resolve the paradox of the lek, and we suggest avenues for future research.
Ταφικές πρακτικές στην Ανατολική Κρήτη κατά την 3η και τις αρχές της 2ης χιλιετίας π.Χ.
Authors: Κιορπέ Σωτηρία
Published: January 2024

Η παρούσα διδακτορική διατριβή πραγματεύεται τον τρόπο μεταχείρισης των νεκρών στο ταφικό εθιμοτυπικό της προανακτορικής και παλαιοανακτορικής περιόδου στην Κρήτη μέσα από τη συστηματική μελέτη των ανθρώπινων σκελετικών καταλοίπων από το νεκροταφείο στη θέση Κεφάλα Πετρά Σητείας στην ανατολική Κρήτη. Κεντρικό ζητούμενο αποτελεί αφενός η ανασύσταση των βιολογικών ιδιοτήτων του πληθυσμού αφετέρου η προσέγγιση του ταφικού εθιμοτυπικού, ειδικότερα των μεταποθετικών πρακτικών μεταχείρισης του νεκρού σώματος. Αρχικα, υιοθετώντας μια «βιογραφική» προσέγγιση, διερευνάται η δημογραφική σύνθεση (αριθμός, φύλο, ηλικία) και τα επίπεδα υγείας της εκάστοτε κοινωνικής ομάδας (ανά ταφικό κτίριο) καθώς και του συνόλου του πληθυσμού του Πετρά. Ακολουθεί η εξέταση των ταφονομικών διαδικασιών και η διάκριση των φυσικών από τους ανθρωπογενείς ταφονομικούς παράγοντες που επέδρασαν στις αποθέσεις των οστών με στόχο την ανασύσταση της μορφής και της ποικιλίας των ταφικών πρακτικών όπως και της συχνότητας και της αλληλουχίας των ταφικών επεισοδίων. Περαιτέρω, μελετώνται οι τρόποι μεταχείρισης των υπόλοιπων υλικών καταλοίπων έχοντας ως βασική επιδίωξη την κατανόηση του ευρύτερου φάσματος των ενσώματων πρακτικών και των κοινωνικών προεκτάσεων τους. Για την επίτευξη των παραπάνω στόχων υιοθετήθηκε ένα συνθετικό μεθοδολογικό και ερμηνευτικό σχήμα που βασίζεται στην συνεξέταση ανθρωπολογικών, ταφονομικών και αρχαιολογικών πληροφοριών. Συνολικά εξετάστηκαν 23.182 θραύσματα οστών από πέντε ταφικά κτίρια εκ των οποίων τα τρία χρησιμοποιήθηκαν αποκλειστικά κατά την προανακτορική περίοδο, το ένα κατά την παλαιοανακτορική και ένα κατά τη διάρκεια και των δύο περιόδων. Από την ταφονομική και οστεολογική ανάλυση των δεδομένων προέκυψε ότι η πλειονότητα των ταφικών αποθέσεων στα ταφικά κτίρια στον Πετρά έχει υποστεί κάποιου είδους δευτερογενή μεταχείριση η οποία είχε ως αποτέλεσμα τη δημιουργία αναμεμειγμένων και διάσπαρτων σωρών οστών. Παρ’ όλα αυτά, η αλληλεπίδραση με τα σώματα/οστά ποικίλλει ανά ταφικό κτίριο και περίοδο καθώς διαπιστώνονται διαφοροποιήσεις ως προς τη μορφή, τη θέση, την επιμέλεια και τη διαχείριση των αποθέσεων. Οι διάφορες πρακτικές μεταχείρισης των σκελετικών καταλοίπων φανερώνουν τον πολυδιάστατο και ρευστό χαρακτήρα της αλληλεπίδρασης και καταδεικνύουν τη σκόπιμη προσπάθεια αλλοίωσης των ατομικών ταυτοτήτων εξασφαλίζοντας το πέρασμα των νεκρών στον κόσμο των προγόνων και την ιδεολογική συνέχεια της κοινότητας του Πετρά.