bluuebunny/crossref_metadata_2025 huggingface dataset:
Patients With Subacute Sclerosing Panencephalitis in Japan: A 2022 Nationwide Survey
Authors: Okabe Hisao , Hashimoto Koichi , Norito Sakurako , Kume Yohei , Chishiki Mina , Hasegawa Shunji , Sakai Yasunari , Nomura Keiko , Shibata Takashi , Suzuki Yasuhiro , Sunagawa Tomimasa , Takao Masaki , Hosoya Mitsuaki
Published: December 2023

Background:

In Japan, the incidence of subacute sclerosing panencephalitis (SSPE) has reduced; however, the medical conditions and factors associated with disease progression remain unclear.

Methods:

A nationwide survey of SSPE was conducted using a questionnaire in 2022. We conducted a descriptive analysis of the patients with SSPE in 2022 and Cox proportional hazards analyses for disease progression. We compared the patients with SSPE with those in a 2007 survey.

Results:

A total of 37 surviving patients with SSPE were enrolled [median age: 32 years (range: 16–52 years)]. No new cases have been identified since 2017 in the survey. Jabbour stage IV was the most common stage (66.7%). The hazard ratios (95% confidence intervals) of male sex and age at the time of measles infection (years) were 2.56 (1.13–5.76) and 0.57 (0.34–0.93), respectively. Compared with those in 2007, the proportion of patients in hospitals decreased from 13.7% to 2.7%, whereas that of patients in nursing facilities increased from 17.6% to 29.7%. The proportions of patients prescribed inosine pranobex, interferon and ribavirin at the time of the survey decreased from 96.1% to 79.4%, 74.8% to 14.3% and 25.3% to 0%, respectively. The proportions of patients with gastrostomy, tracheostomy and ventilator use increased from 5.9% to 69.7%, 23.3% to 60.0% and 10.8% to 32.4%, respectively.

Conclusions:

Decreased measles cases in Japan reduced new SSPE cases. However, surviving patients in 2022 had advanced disease stages and needed medical care. Male sex and early measles infection were significantly associated with disease progression.
Plexiform Schwannoma of the Eyelid
Authors: Pietris James , James Craig , Patel Sandy , Selva Dinesh
Published: December 2023

Plexiform schwannoma of the lacrimal gland of the palpebral lobe has not been previously described. This 41-year-old male presented with a 2-year history of a left upper eyelid mass and associated regional irritation. MRI of the head and orbits confirmed a left superolateral multinodular mass centered on the palpebral lobe of the left lacrimal gland. Excision revealed a schwannoma of the plexiform subtype.
Therapeutic plasma exchange in critical illness
Authors: Koniman Riece , Kaushik Manish
Published: December 2023

Therapeutic plasma exchange (TPE) is widely used for various diseases, particularly in critically ill patients. Most of these indications rely mainly on the removal of pathological molecules in the plasma by TPE. TPE is also used to replace missing plasma components in some diseases. However, there are emerging data on the use of TPE in novel indications because of its potential immunomodulatory effects. This review discusses the techniques of TPE, key considerations when prescribing TPE, indications for TPE in critically ill patients, emerging developments and knowledge gaps in this field.
Research hotspots and trends in the relationship between genetics and major depressive disorder: A scientometric analysis from 2003 to 2023
Authors: Zhao Ziwei , Li Yanyan , Wang Peili , Zhang Ran , Nie Zhongbiao
Published: December 2023

To determine current research objectives and predict future trends in studies on the relationship between genetics and major depressive disorder (MDD). We collected the publications in the last 20 years (2003–2023) related to genetics and MDD in the Web of Science database, and applied Citespace to assess the knowledge mapping. The number of manuscripts about genetics and MDD totaled 9200, with a faster increase after 2013. The country, institution, and author with the most publications are the USA, the University of London, and Serretti, Alessandro. BIOL PSYCHIAT published the most articles in this field. In addition, the most co-cited reference is Sullivan PF (2000) (673). Genetic and MDD research, including the hippocampus, and HPA axis may become the focus of research in the future. Based on a 20-year scientometric investigation, we know the USA, China, and Germany have emerged as the important research forces in this discipline. The strongest collaborations between developed countries and renowned institutions are beneficial to the advancement of genetic and MDD research. Serotonin is the strongest citation bursts keyword.
Research progress on the treatment of perimenopausal insomnia with Chaihu Jia Longgu Muli decoction based on brain-intestine-bacteria axis: A review
Authors: Wang Yaolei , Guan Ruiqian , Zhong Jifa , Shi Qingchun , Ye Ziyu , Pan Limin
Published: December 2023

With the progress and rapid societal development, women are confronted with multifaceted pressures in their lives, encompassing familial and other domains. Furthermore, during the perimenopausal phase, endocrine equilibrium is disrupted, leading to the emergence of psychological and physiological health challenges. Insomnia is a prevalent symptom among perimenopausal individuals. The brain-gut-bacteria axis assumes a pivotal role in the prevention, diagnosis, and management of perimenopausal insomnia. Chaihu Jia Longgu Muli decoction is a commonly prescribed remedy for addressing perimenopopausal insomnia. Consequently, this paper aims to investigate the interplay between the brain-gut-bacteria axis, intestinal microbiota, and the pathogenesis of perimenopausal insomnia. The study focuses on examining the regulatory effects of Chaihu Jia Longgu Muli decoction on the nervous system, intestinal microbiota, and the hypothalamus-pituitary-adrenal axis. Additionally, it explores the mechanisms underlying Hujia Longgu Muli decoction in mitigating perimenopausal insomnia.
Comparison of the effects of stepwise intracranial decompression and decompressive craniectomy in the treatment of severe traumatic brain injury: A randomized controlled trial
Authors: Liu Chunbo , Jia Geng , Wu Ruhong , Yang Changchun
Published: December 2023

Background:

To compare the effects of stepwise intracranial decompression (SID) and decompressive craniectomy (DC) on severe traumatic brain injury.

Methods:

This prospective randomized study was conducted at The Third Affiliated Hospital of Soochow University. Ninety two patients were divided into 2 groups according to the random number table method. The study group received SID, whereas the control group received DC. The surgical time and intraoperative bleeding of the 2 groups of patients were recorded, neurological function and glasgow coma score before and after treatment in both groups, incidence of complications, prognostic situation, and levels of brain oxygen metabolism indicators before and after treatment.

Results:

Among the 92 patients who agreed, 46 were assigned to the study and control groups, and 6 patients were excluded. Finally, 86 patients were analyzed, including 43 in the study group and 43 in the control group. After treatment, the glasgow coma score scores of the 2 groups increased compared to before treatment; the study group had a higher score, The National Institutes of Health Stroke Scale score decreased compared to before treatment, and the study group had a lower score (P < .05). The incidence of complications in the study group (4.65%) was significantly lower than that in the control group (18.60%) (P < .05). The good prognosis rate of the research group (41.86%) was significantly higher than that of the control group (16.28%) (P < .05).

Conclusion:

Compared with DC, using SID to treat severe traumatic brain injury can shorten surgical time and reduce intraoperative bleeding, more effectively improve patients neurological function and consciousness state, reduce the incidence of complications, and regulate brain oxygen metabolism status, which is beneficial for improving prognosis and ensuring a good outcome of the disease.
Association between carotenoid intake and metabolic dysfunction-associated fatty liver disease among US adults: A cross-sectional study
Authors: Zhang Hang , Li Li , Jia Lei , Liu Jinchun
Published: December 2023

Carotenoids have been recognized for their potential health benefits due to their antioxidant properties. There is limited research on the association between metabolic dysfunction-associated fatty liver disease (MAFLD) and carotenoids. This study aimed to investigate the effect of carotenoid intake on the risk of MAFLD. We retrospectively analyzed 2722 adults aged ≥ 18 from the National Health and Nutrition Examination Survey 2017-2018. Hepatic steatosis was identified by elastography, and carotenoid consumption was evaluated through two 24-hour dietary recall interviews. Weighted logistic regression models, subgroup analyses, and restricted cubic splines were used for analyses. The weighted prevalence of MAFLD was 51.90%. Weighted logistic regression analysis demonstrated that intake of β-carotene, lutein/zeaxanthin, and lycopene was associated with a lower risk of MAFLD after adjusting for various covariates. Compared to the lowest tertile, a significant inverse correlation was observed between the highest total lycopene intake and MAFLD among females in the gender subgroup analysis. Restricted cubic spline regression analysis revealed a U-shaped association between lycopene consumption and MAFLD risk (P < .001), with an inflection point of approximately 9.48 mg/day. Moreover, the nonlinear relationship was particularly significant in females and absent in males. In summary, increased β-carotene, lutein/zeaxanthin, and lycopene consumption was associated with a decreased risk of MAFLD. The relationship between total lycopene intake and MAFLD was nonlinear, primarily in females. These findings have significant implications for the potential prevention and management of MAFLD.
A novel nomogram for predicting risk of hypertension in US adults with periodontitis: National Health and Nutrition Examination Survey (NHANES) 2009–2014
Authors: Wang Yicheng , Ni Binghang , Xiao Yuan , Lin Yichang , Zhang Yan
Published: December 2023

The goal of our study was to create a nomogram to predict the risk of developing hypertension in patients with periodontitis. Our study used data from a total of 3196 subjects from the National Health and Nutrition Examination Survey 2009 to 2014 who had ever been diagnosed with periodontitis. The data set was randomly divided into a training set and a validation set according to a 7:3 ratio. The data from the training set was utilized to build the prediction model, while the validation set were used to validate the model. To identify the risk variables, stepwise regression was used to perform successive univariate and multivariate logistic regression analysis. The predictive ability of the nomogram model was evaluated using receiver operating characteristic curve. Calibration plots were used to assess the consistency of the prediction model. The clinical value of the model was evaluated using decision curve analysis and clinical impact curve. A nomogram for the risk of hypertension in subjects with periodontitis was constructed in accordance with the 8 predictors identified in this study. The areas under the receiver operating characteristic curve values for the training set and validation set were 0.922 (95% confidence interval: 0.911–0.933) and 0.918 (95% confidence interval: 0.900–0.935), respectively, indicating excellent discrimination. The decision curve analysis and clinical impact curve suggested that the model has significant clinical applications, and the calibration plots of the training set and validation set demonstrated good consistency. The nomogram can effectively predict the risk of hypertension in patients with periodontitis and help clinicians make better clinical decisions.
Real-world analysis of integration of sacubitril/valsartan into clinical practice in Saudi Arabia
Authors: Badreldin Hisham A. , Korayem Ghazwa B. , Alenazy Basel A. , Aljohani Mousa H. , Alshaya Omar A. , Al Sulaiman Khalid , Alabdelmuhsin Lolwa , Alenazi Huda , Almutairi Dahlia M. , Alanazi Faisal , Alobathani Seba K. , Alqannam Ghada M. , Almadani Ohoud , Aljuhani Ohoud , Hafiz Awatif , Aljowaie Ghalyah , Basha Ehssan , Alqahtani Tariq , Alhussein Mosaad
Published: December 2023

Despite the demonstrated advantages of angiotensin receptor/neprilysin inhibitors in the management of heart failure, the pivotal Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure (PARADIGM-HF) trial, which explored this class of medications, did not include individuals from Saudi Arabia. Recognizing that different nations and ethnic groups may exhibit unique characteristics, this study aimed to compare the demographics and outcomes of patients in Saudi Arabia who received sacubitril/valsartan (Sac/Val) with those enrolled in the PARADIGM-HF trial. In this retrospective, multicenter cohort study, we included all adult patients diagnosed with heart failure with reduced ejection fraction (HFrEF) within a tertiary healthcare system in Saudi Arabia between January 2018 and December 2021 and were initiated on Sac/Val. The primary objective was to compare the patient characteristics of those initiating Sac/Val treatment with the participants in the PARADIGM-HF trial. The secondary endpoints included the initiation setting, dose initiation, and titration, as well as alterations in B-type natriuretic peptide and ejection fraction at the 6-month mark. Furthermore, we reported the hospitalization and mortality event rates at the 12-month time point. The study included 400 patients with HFrEF receiving Sac/Val. Compared with the PARADIGM-HF trial, the cohort had a younger mean age and a higher prevalence of diabetes mellitus. SAC/VAL was prescribed as the initial therapy for 34% of the patients, while the remaining participants were initially treated with either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker before transitioning to Sac/Val. Approximately 75% of patients were initiated on 100 mg Sac/Val twice daily, and 90% initiated therapy in the inpatient setting. The mean ejection fraction significantly improved from 26.5 ± 8.4% to 30.5 ± 6.4% at 6 months (P < .001), while the median B-type natriuretic peptide level change was not significant (P = .39). Our study revealed notable disparities in the baseline characteristics of patients with HFrEF compared with those in the PARADIGM-HF trial. These findings offer valuable real-world insights into the prescription patterns and outcomes of Sac/Val in patients with HFrEF in Saudi Arabia, an aspect not previously represented in the PARADIGM-HF study.
The association of traditional obesity parameters with the length of stay among patients with coronary artery disease: A cross-sectional study
Authors: Hayajneh Audai A. , Alhusban Islam M. , Rababa Mohammad , Al-sabbah Shatha , Bani-Hamad Dania , Al-Mugheed Khalid , Al-Nusour Esraa A. , Alsatari Eman S.
Published: December 2023

There is a strong association between obesity and coronary artery disease (CAD). Obesity is measured using traditional obesity parameters, such as body mass index, body adiposity index, waist circumference (WC), and hip circumference. The aim of this study is to explore the association between traditional obesity parameters and the length of stay (LOS) among hospitalized CAD patients. An original correlative descriptive study was carried out using secondary data analysis, in which 220 hospitalized Jordanian CAD patients were recruited from Jordan northern and middle regions. Age, WC, triglycerides, and high- sensitivity C-reactive protein were all positive predictors of the total hospital LOS among hospitalized patients with CAD. The WC, age, triglycerides, and high-sensitivity C-reactive protein levels were significantly positively associated with total LOS. Healthcare providers, including nurses, should take into account these significant positive predictors of LOS to achieve better health outcomes and improve patient satisfaction.
Intraoperative cone-beam computed tomography-guided curettage for osteoid osteoma
Authors: Tsuha Yuichi , Oshiro Hiromichi , Mizuta Kohei , Aoki Yusuke , Tamaki Tomoko , Wada Naoki , Tome Yasunori , Nishida Kotaro
Published: December 2023

Recently, cone-beam computed tomography (CBCT)-guided surgeries have been developed for bone and soft tissue tumors. The present study aimed to evaluate the efficacy of CBCT-guided curettage for osteoid osteoma. Our study population included 13 patients who underwent primary curettage for osteoid osteoma using intraoperative CBCT in a hybrid operating room between April 2019 and November 2022. We collected the following data: sex, age, follow-up period, symptom onset to time of surgery, tumor size and location, length of skin incision, operating time, radiation dose, recurrence, postoperative complications, and visual analog scale for pain during the last follow-up. There were 10 male and 3 female patients, and the mean age was 25.0 years (range, 9–49 years). The mean follow-up period was 10.6 months (range, 0.4–24.0 months). The locations of the tumors were the proximal femur in 6 patients, the acetabular region in 2 patients, and the ilium, tibial shaft, calcaneus, cuboid, and talus in 1 patient each. The mean time of symptoms onset to surgery was 18.7 months (range, 2.3–69.9 months). The mean maximum diameter of the tumor was 5.9 mm (range, 3.5–10.0 mm). The mean length of the skin incision was 2.2 cm (range, 1.5–3.5 cm). The mean operating time was 96.9 minutes (range, 64–157 minutes). The mean dose of radiation was 193.2 mGy (range, 16.3–484.0 mGy). No recurrences, postoperative complications, and reoperation were observed in this study. All the patients reported 0 mm on the visual analogue scale for pain on the last follow-up. CBCT-guided curettage for osteoid osteoma was minimally invasive and reliable. This procedure can be effective for the treatment of lesions found in deep locations such as the pelvic bone and proximal femur or an invisible lesion that cannot be detected by regular fluoroscopy.
The effects of esketamine on blood pressure and hypotension incidence during induction of bariatric surgery: A randomized controlled trial
Authors: Yang Ting , Mudabbar Muhammad Saqib , Xu Mingxing , Xiang Qingmei , Liu Bin , Fu Qiang
Published: December 2023

Background:

The prevalence of obesity is high. Bariatric surgery is an effective treatment for severe obesity; however, the induction phase of anesthesia in these patients poses a risk of hypotension. Esketamine, known for its sympathetic nervous system stimulation, may stabilize blood pressure during induction. This study aimed to investigate the effects of esketamine on blood pressure in bariatric surgery patients.

Methods:

This randomized controlled trial included 145 patients undergoing bariatric surgery. Patients were randomly assigned to receive esketamine or a control intervention during induction. Blood pressure and other vital signs were measured and compared between the 2 groups using statistical analyses.

Results:

Administration of esketamine increased blood pressure before intubation (T2). The incidence of hypotension was lower in the esketamine group at multiple time points during induction. Postoperatively, the esketamine group exhibited lower pain scores at 24 hours and a reduced need for rescue analgesics.

Conclusion:

A single dose of 0.2 mg/kg esketamine during the induction phase of bariatric surgery can improve blood pressure stability and decrease the incidence of hypotension. Furthermore, it is associated with reduced postoperative pain. Future studies could explore the effects of higher esketamine doses and validate these findings in a larger and more diverse patient population.
Home-based tele-rehabilitation versus hospital-based outpatient rehabilitation for pain and function after initial total knee arthroplasty: A systematic review and meta-analysis
Authors: Zhang Hui , Wang Junqing , Jiang Zekun , Deng Tao , Li Kang , Nie Yong
Published: December 2023

Background:

This systematic review and meta-analysis aims to compare the effectiveness of home-based tele-rehabilitation programs with hospital-based rehabilitation programs in improving pain and function at various time points (≤6 weeks, ≤14 weeks, and ≤ 52 weeks) following the initial total knee arthroplasty.

Methods:

This study used PRISMA and AMSTAR reporting guidelines. We systematically searched 5 databases (PubMed, Embase, Web of Science, Cochrane Library, and Medline) to identify randomized controlled trials published from January 1, 2019, to January 1, 2023. The primary outcomes were pain, knee injury and osteoarthritis outcome score, and mobility (knee range of motion).

Results:

We included 9 studies involving 1944 patients. Low-quality evidence showed hospital-based rehabilitation was better than home-based tele-rehabilitation in knee injury and osteoarthritis outcome score (mean difference [MD], −2.62; 95% confidence interval [CI], −4.65 to −0.58; P = .01) at ≤ 14 weeks after total knee arthroplasty. Based on low-quality evidence, home-based tele-rehabilitation was better than hospital-based rehabilitation in knee range of motion (MD, 2.00; 95% CI, 0.60 to 3.40; P = .005). There was no significant difference between hospital-based rehabilitation and home-based tele-rehabilitation in knee pain at ≤ 6 weeks (MD, 0.18; 95% CI, −0.07 to 0.42; P = .16), 14 weeks (MD, 0.12; 95% CI, −0.26 to 0.49; P = .54), and ≤ 52 weeks (MD, 0.16; 95% CI, −0.11 to 0.43; P = .24).

Conclusion:

Home-based tele-rehabilitation and hospital-based rehabilitation programs showed comparable long-term outcomes in pain, mobility, physical function, and patient-reported health status after primary total knee arthroplasty. Considering the economic costs, home-based tele-rehabilitation programs are recommended as a viable alternative to hospital-based rehabilitation programs.
The vagus nerve cross-sectional area on ultrasound in patients with type 2 diabetes
Authors: Kotb Mamdouh Ali , Bedewi Mohamed A. , Almalki Daifallah Mohamed , AlAseeri Ali Abdullah , Alhariqi Bader A. , Soliman Steven B. , Aldossary Nasser M. , Aboulela Wael Hamed
Published: December 2023

Diabetic neuropathy, including autonomic neuropathy is a serious complication related to type 2 diabetes mellitus (T2D). The vagus nerve (VN) is the longest nerve in the autonomic nervous system, and since diabetic neuropathy manifests first in longer nerves, the VN is commonly affected in early diabetic autonomic neuropathy. The use of high-resolution ultrasound for peripheral and cranial nerve imaging has significantly increased over the past 2 decades. The aim of the study is to compare the cross-sectional area of the VN in patients with T2D to that of a control cohort without T2D. A total of 52 VN cross-sectional areas were recorded from patients with T2D. A total of 56 VN cross-sectional areas were also recorded from asymptomatic subjects without T2D. In each subject, high-resolution ultrasound imaging of the bilateral VNs was performed in the short-axis between the common carotid artery and the internal jugular vein. The VN cross-sectional areas were recorded and compared. In the patients with T2D, HbA1c and fasting blood glucose levels were obtained as well as the duration of T2D in years and correlated with the cross-sectional areas. The bilateral VN cross-sectional areas were similar in both cohorts. Additionally, no correlation was seen between the VN cross-sectional areas, demographics, or clinical data of T2D. Our study demonstrated normal VN cross-sectional areas in patients with T2D without any significant relation with the patients’ demographic or clinical data.
Combined gastric and colorectal cancer endoscopic screening may be cost-effective in Europe with the implementation of artificial intelligence: an economic evaluation
Authors: Libanio Diogo , Antonelli Giulio , Marijnissen Fleur , Spaander Maanon CW , Hassan Cesare , Dinis-Ribeiro Mario , Areia Miguel
Published: December 2023

Background/aims

Endoscopic screening for gastric cancer (GC) is not recommended in low-intermediate incidence countries. Artificial intelligence (AI) has high accuracy in GC detection and might increase the cost-effectiveness of screening strategies. We aimed to assess the cost-effectiveness of AI for GC detection in settings with different GC incidence and different accuracies of AI systems.

Methods

Cost-effectiveness analysis (using Markov model) comparing different screening strategies (no screening versus single esophagogastroduodenoscopy (EGD) at 50 years versus stand-alone EGD every 5/10 years versus combined EGD and screening colonoscopy once or twice per decade in Netherlands, Italy and Portugal) with variable AI accuracy settings. The primary outcome was the incremental cost-effectiveness ratio of the different strategies versus no screening. Deterministic and probabilistic sensitivity analyses were conducted.

Results

Without AI, one single EGD at 50 years (Netherlands, Italy, Portugal), EGD combined with screening colonoscopy once per decade (Italy and Portugal) and EGD combined with screening colonoscopy twice per decade (Portugal) are cost-effective when compared with no screening. If AI increases the accuracy of EGD by at least 1% in comparison to the accuracy of white-light endoscopy accuracy (89%), combined screening twice per decade also becomes cost-effective in Italy. If AI accuracy reaches at least 96%, combined screening once per decade is also cost-effective in the Netherlands.

Discussion

In European countries, AI-assisted EGD may improve the cost-effectiveness of GC screening with combined EGD and screening colonoscopy. The actual effect of AI on cost-effectiveness may vary dependent on the accuracy and costs of the AI system.
Noonan Syndrome–related Myeloproliferative Disorder Occurring in the Neonatal Period: Case Report and Literature Review
Authors: Hoshino Yuki , Moriya Kunihiko , Mitsui-Sekinaka Kanako , Hashimoto Yu , Nakayama Satoshi , Sajiki Daichi , Muramatsu Hideki , Hagiwara Hidetoshi , Suzuki Shuichi , Sekinaka Yujin , Wakamatsu Hajime , Kawaguchi Hiroyuki , Imai Kohsuke
Published: December 2023

Noonan syndrome–related myeloproliferative disorder (NS/MPD) and juvenile myelomonocytic leukemia (JMML) are rare MPDs that occur in young children. We herein report a case of NS/MPD with neonatal onset. The patient had a characteristic appearance and high monocyte count in the peripheral blood and bone marrow. Genetic testing showed the E139D mutation in PTPN11; however, the patient did not meet all the diagnostic criteria for JMML, and we thus diagnosed him with NS/MPD. Eight other cases of NS/MPD with neonatal onset are also summarized. The initial presentation varied, and the prognosis was considered poor compared with previous reports of NS/MPD.
Preexposure prophylaxis availability among health facilities participating in the global International epidemiology Databases to Evaluate AIDS (IeDEA) consortium
Authors: Kebede Samuel , Brazier Ellen , Freeman Aimee M. , Muwonge Timothy R. , Choi Jun Yong , de Waal Renee , Poda Armel , Cesar Carina , Munyaneza Athanase , Kasozi Charles , Pasayan Mark Kristoffer U. , Althoff Keri N. , Shongo Alisho , Low Nicola , Ekouevi Didier , Veloso Valdiléa G. , Ross Jonathan
Published: December 2023

Background:

While recognized as a key HIV prevention strategy, preexposure prophylaxis (PrEP) availability and accessibility are not well documented globally. We aimed to describe PrEP drug registration status and the availability of PrEP services across HIV care sites participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium.

Methods:

We used country-level PrEP drug registration status from the AIDS Vaccine Advocacy Coalition and data from IeDEA surveys conducted in 2014, 2017 and 2020 among participating HIV clinics in seven global regions. We used descriptive statistics to assess PrEP availability across IeDEA sites serving adult patients in 2020 and examined trends in PrEP availability among sites that responded to all three surveys.

Results:

Of 199 sites that completed the 2020 survey, PrEP was available in 161 (81%). PrEP availability was highest at sites in North America (29/30; 97%) and East Africa (70/74; 95%) and lowest at sites in Central (10/20; 50%) and West Africa (1/6; 17%). PrEP availability was higher among sites in countries where PrEP was officially registered (146/161; 91%) than where it was not (14/32; 44%). Availability was higher at health centers (109/120; 90%) and district hospitals (14/16; 88%) compared to regional/teaching hospitals (36/63). Among the 94 sites that responded to all three surveys, PrEP availability increased from 47% in 2014 to 60% in 2017 and 76% in 2020.

Conclusion:

PrEP availability has substantially increased since 2014 and is now available at most IeDEA sites. However, PrEP service provision varies markedly across global regions.
Variations in the results of nutritional epidemiology studies due to analytic flexibility: Application of specification curve analysis to red meat and all-cause mortality
Authors: Wang Yumin , Pitre Tyler , Wallach Joshua D. , de Souza Russell J. , Jassal Tanvir , Bier Dennis , Patel Chirag J. , Zeraatkar Dena
Published: December 2023

Objective

To present an application of specification curve analysis—a novel analytic method that involves defining and implementing all plausible and valid analytic approaches for addressing a research question—to nutritional epidemiology.

Data source

National Health and Nutrition Examination Survey (NHANES) 2007 to 2014 linked with National Death Index.

Methods

We reviewed all observational studies addressing the effect of red meat on all-cause mortality, sourced from a published systematic review, and documented variations in analytic methods (e.g., choice of model, covariates, etc.). We enumerated all defensible combinations of analytic choices to produce a comprehensive list of all the ways in which the data may reasonably be analyzed. We applied specification curve analysis to NHANES data to investigate the effect of unprocessed red meat on all-cause mortality, using all reasonable analytic specifications.

Results

Among 15 publications reporting on 24 cohorts included in the systematic review on red meat and all-cause mortality, we identified 70 unique analytic methods, each including different analytic models, covariates, and operationalizations of red meat (e.g., continuous vs. quantiles). We applied specification curve analysis to NHANES, including 10,661 participants. Our specification curve analysis included 1,208 unique analytic specifications. Of 1,208 specifications, 435 (36.0%) yielded a hazard ratio equal to or above 1 for the effect of red meat on all-cause mortality and 773 (64.0%) below 1, with a median hazard ratio of 0.94 [IQR: 0.83 to 1.05]. Forty-eight specifications (3.97%) were statistically significant, 40 of which indicated unprocessed red meat to reduce all-cause mortality and 8 of which indicated red meat to increase mortality.

Conclusion

We show that the application of specification curve analysis to nutritional epidemiology is feasible and presents an innovative solution to analytic flexibility.

Limitations

Alternative analytic specifications may address slightly different questions and investigators may disagree about justifiable analytic approaches. Further, specification curve analysis is time and resource-intensive and may not always be feasible.
A systematic review and meta-analysis of school-based preventive interventions targeting e-cigarette use among adolescents
Authors: Gardner Lauren A. , Rowe Amy-Leigh , Newton Nicola C. , Egan Lyra , Hunter Emily , Devine Emma K. , Aitken Tess , Thornton Louise , Teesson Maree , Stockings Emily , Champion Katrina E.
Published: December 2023

Objective

To examine the efficacy of school-based e-cigarette preventive interventions via a systematic review and meta-analysis.

Data sources

We searched MEDLINE, Embase, PsycINFO, Scopus, CINAHL, Cochrane and clinical trials registries for studies published between January 2000-June 2023 using keywords for e-cigarettes, adolescents, and school.

Study selection

Of 1566 double-screened records, 11 met criteria of targeting adolescents, evaluating an e-cigarette preventive intervention, being conducted in a secondary school, using a randomised controlled trial (RCT), cluster RCT or quasi-experimental design, and comparing an intervention to a control.

Data extraction

Pre-specified data pertaining to the study design, outcomes, and quality were extracted by one reviewer and confirmed by a second, and where necessary, third reviewer.

Data synthesis

Our narrative synthesis showed some school-based interventions prevented or reduced e-cigarette and/or tobacco use, however some increased use. Meta-analyses on a subsample of studies found that, overall, school-based interventions were not associated with the prevention of e-cigarette (OR=0.43, 95%CI=0.16, 1.12; p=0.09) or tobacco (OR=1.01, 95%CI=0.65, 1.59, p=0.95) use, however were associated with reductions in past 30-day tobacco use (OR=0.59, 95%CI=0.39, 0.89, p=0.01) which encompassed e-cigarettes in some studies. School-based interventions were also associated with improved knowledge (SMD=-0.38, 95%CI=-0.68, -0.08, p=0.01), intentions (SMD=-0.15, 95%CI=-0.22, -0.07, p=0.0001), and attitudes (SMD=-0.14, 95%CI=-0.22, -0.06; p=0.0007) in the short-term. Overall, the quality of evidence was low-to-moderate.

Conclusions

School-based interventions hold potential for addressing e-cigarette use, however, can have null or iatrogenic effects. More high-quality research is needed to develop efficacious interventions, and schools must be supported to adopt evidence-based programs.
LEPROSY RELAPSE AFTER POLYCHEMOTHERAPY: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Verônica da Silva Fabiane , Santos de Sousa Gutembergue , Ferreira Elena Alves Benevides , de Souza Silva Pãmela Rodrigues , Takahashi Juliana Akie , Espinosa Omar Ariel , Ignotti Eliane , Olmo Roberta Pinheiro , de Araújo Püschel Vilanice Alves , Anastácio Zélia Ferrreira Caçador , Ferreira Silvana Margarida Benevides
Published: December 2023

Objective: To synthesize the best scientific evidence related to estimating the prevalence of leprosy relapse cases after polychemotherapy treatment.Method:A systematic review was conducted following the JBI methodology for systematic reviews of prevalence studies, and the reporting stage adhered to PRISMA-P, with registration No.: CRD42020177141. The inclusion criteria were adopted following the PopCoCo mnemonic (Population, Condition, Context). Population: people of both genders and any age, diagnosed with leprosy relapse, and treated with paucibacillary or multibacillary therapeutic regimes. Condition: leprosy relapse after Polychemotherapy (PCT) estimated as a proportion of cases.Context: studies conducted within the scope of health services. Databases used: Medline, LILACS, Embase, CINAHL, Scopus, WoS, CARPHA; Mendeley reference manager. A random-effects meta-analysis model was applied, and heterogeneity was assessed using the Higgins test.Results: Out of 41 studies included in the review, involving a total of 93,461 patients with leprosy, 4.09% (n=3,830) were eligible for relapse after polychemotherapy. Of them, 69.71% (n=2,670) were treated both with multibacillary and with paucibacillary regimes (72.36%, n=1,932; and 27.64%, n=738, respectively), and with a bacilloscopy index ≥4. Relapse prevalence was observed in males and in people aged over 30 years old. The meta-analysis estimated the global prevalence of leprosy relapse at 11% (95%CI: 0.09-0.12), with higher prevalence rates in Brazil (31%) and India (13%).Conclusion: There is evidence of high global prevalence of leprosy relapse after PCT, with higher estimates in India and Brazil, countries burdened with higher prevalence of the disease.

SYNTHESIS

Although leprosy us an ancient disease with a scientifically proven effective treatment, it remains a Public Health problem. This is not only due to the disease high prevalence but also to its potential to cause physical disabilities, leading to emotional and social impacts and, consequently, compromising quality of life. In addition to the new cases of the disease, another concern commonly reported in the literature is leprosy relapse after polychemotherapy, as it has repercussions on therapeutic effectiveness. The relapse causes are usually associated with therapeutic failure due to incomplete treatment, misclassification in the initial treatment, and multidrug resistance. This study provides insights to verify the disease current prevalence based on scientific evidence, which can contribute to expanding the prevention strategies.
MOCAT: Multi-Omics Integration with Auxiliary Classifiers Enhanced Autoencoder
Authors: Yao Xiaohui , Jiang Xiaohan , Luo Haoran , Liang Hong , Ye Xiufen , Wei Yanhui , Cong Shan
Published: December 2023

Background

Integrating multi-omics data is emerging as a critical approach in enhancing our understanding of complex diseases. Innovative computational methods capable of managing high-dimensional and heterogeneous datasets are required to unlock the full potential of such rich and diverse data.

Methods

We propose a Multi-Omics integration framework with auxiliary Classifiers-enhanced AuToencoders (MOCAT), for comprehensive utilization of both intra- and inter-omics information. Additionally, attention mechanisms with confidence learning are incorporated for enhanced feature representation and trustworthy prediction.

Results

Extensive experiments were conducted on four benchmark datasets to evaluate the effectiveness of our proposed model, including BRCA, ROSMAP, LGG, and KIPAN. Our model significantly improved most evaluation measurements and consistently surpassed the state-of-the-art methods. Ablation studies showed that the auxiliary classifiers significantly boosted classification accuracy in both the ROSMAP and LGG datasets. Moreover, the attention mechanisms and confidence evaluation block contributed to improvements in the predictive accuracy and generalizability of our model.

Conclusions

The proposed framework exhibits superior performance in disease classification and biomarker discovery, establishing itself as a robust and versatile tool for analyzing multi-layer biological data. This study highlights the significance of elaborated designed deep learning methodologies in dissecting complex disease phenotypes and improving the accuracy of disease predictions.
COMBINED EFFECTS OF AMBIENT TEMPERATURE AND FOOD AVAILABILITY ON INDUCED INNATE IMMUNE RESPONSE OF A FRUIT-EATING BAT (CAROLLIA PERSPICILLATA)
Authors: Viola Matheus F. , Herrera M. L. Gerardo , Cruz Ariovaldo P.
Published: December 2023

Resilience of mammals to anthropogenic climate and land-use changes is associated with the maintenance of adequate responses of several fitness-related traits such as those related to immune functions. The combined effects of decrease in food availability (Fa) and an increase in ambient temperature (Ta) can lead to immunosuppression and greater susceptibility to disease. In this study, we measured how selected physiological and behavioral components associated with the innate immune system of fruit-eating bats (Carollia perspicillata) respond to isolated and combined effects of changes in Ta and Fa. We tested the general hypothesis that decreased Fa, increased Ta and the combined effect of both factors would affect bat immune performance. Physiological (fever, leukocytosis and neutrophil/lymphocyte ratio) and behavioral (food intake) components of the acute phase response (APR), as well as bacterial killing ability of the plasma (BKA) were assessed after immune challenge with lipopolysaccharide (LPS: 10 mg/kg) in experimental groups kept at different short-term conditions of Fa (ad libitum diet or 50% food-deprived) and Ta (27 and 33°C). Our results indicate that magnitude of increase in body temperature was not affected by Fa, Ta or the interaction of both factors, but the time to reach the highest increase took longer in LPS-injected bats that were kept under food restriction. The magnitude of increased neutrophil/lymphocyte ratio (N/L) was affected by the interaction between Fa and Ta, but food intake, total white blood cell count and BKA were not affected by any factor or interaction. Overall, our results suggest that BKA and most components of APR examined are not affected by short-term changes in Fa and Ta within the range evaluated in this study, and that the increase of the N/L ratio when bats are exposed to low Fa and high Ta might represent an enhancement of cellular response to deal with infection.
Shieldin and CST co-orchestrate DNA polymerase-dependent tailed-end joining reactions independently of 53BP1-governed repair pathway choice
Authors: King Ashleigh , Reichl Pia , Metson Jean S. , Parker Robert , Munro Daniella , Oliveira Catarina , Becker Jordan R. , Biggs Daniel , Preece Chris , Davies Benjamin , Chapman J. Ross
Published: December 2023

53BP1 regulates DNA end-joining in lymphocytes, diversifying immune antigen receptors. This involves nucleosome-bound 53BP1 at DNA double-stranded breaks (DSBs) recruiting RIF1 and shieldin, a poorly understood DNA-binding complex. The 53BP1-RIF1-shieldin axis is pathological inBRCA1-mutated cancers, blocking homologous recombination (HR) and driving illegitimate non-homologous end-joining (NHEJ). However, how this axis regulates DNA end-joining and HR suppression remains unresolved.

We investigated shieldin and its interplay with CST, a complex recently implicated in 53BP1-dependent activities. Immunophenotypically, mice lacking shieldin or CST are equivalent, with class-switch recombination co-reliant on both complexes. ATM-dependent DNA damage signalling underpins this cooperation, inducing physical interactions between these complexes that reveal shieldin as a DSB-responsive CST adaptor. Furthermore, DNA polymerase ζ functions downstream of shieldin, establishing DNA fill-in synthesis as the physiological function of shieldin-CST. Lastly, 53BP1 suppresses HR and promotes NHEJ in BRCA1-deficient mice and cells independently of shieldin. These findings showcase the resilience of the 53BP1 pathway, achieved through the collaboration of chromatin-bound 53BP1 complexes and DNA end-processing effector proteins.
Unraveling the Impact of W215A/E217A Mutations on Thrombin’s Dynamics and Thrombomodulin Binding through Molecular Dynamics Simulations
Authors: Wu Dizhou , Salsbury Freddie R.
Published: December 2023

Thrombin, a central serine protease in hemostasis, exhibits dual functionality in coagulation processes—favoring fibrinogen cleavage in its native form while shifting towards protein C activation when complexed with thrombomodulin (TM). Thrombin also plays roles in cancer-associated thrombosis and may be involved in metastasis and tumorigenesis. The W215A/E217A (WE) double mutant of thrombin presents a unique case, with its fibrinogen cleavage activity diminished by 19,000-fold, contrasting a modest 7-fold reduction in protein C activation in the presence of TM. The differential substrate specificity of this mutant raises fundamental questions about the underlying molecular mechanisms. In this study, we employed all-atom microsecond-scale molecular dynamics (MD) simulations, complemented by Root Mean Square Fluctuation (RMSF) analysis, clustering algorithms, PCA-based free-energy surfaces, and logistic regression modeling, to dissect the structural and allosteric changes driving thrombin’s substrate specificity. Our results unveil distinct conformational states within the catalytic triad, each optimized for specific substrate interactions. We demonstrate that the WE mutations synergize with TM456 binding, resulting in altered hydrogen bond networks and distinct free energy landscapes. A key finding of our research is the identification of ARG125 as a pivotal element in these interactions, consistently forming critical hydrogen bonds across different thrombin variants. The persistent role of ARG125 not only elucidates aspects of thrombin’s functional plasticity but also positions it as a promising target for novel therapies. This comprehensive analysis enhances our understanding of thrombin’s structural dynamics, paving the way for more effective and targeted therapeutics.
General Anesthesia Activates a Central Anxiolytic Center in the BNST
Authors: Lu Dongye , Choi Seonmi , Park Jaehong , Kim Jiwoo , Zhao Shengli , Uldry Lavergne Camille G. , Desimone Quinn , Chen Bin , Han Bao-Xia , Wang Fan , Goldstein Nitsan
Published: December 2023

Low doses of general anesthetics like ketamine and dexmedetomidine have anxiolytic properties independent of their sedative effects. How these different drugs exert these anxiolytic effects is not well understood. We discovered a population of GABAergic neurons in the oval division of the bed nucleus of the stria terminalis that is activated by multiple anesthetics and the anxiolytic drug diazepam (ovBNSTGA). A majority of ovBNSTGAneurons express neurotensin receptor 1 (Ntsr1) and innervate brain regions known to regulate anxiety and stress responses. Optogenetic activation ovBNSTGAor ovBNSTNtsr1neurons significantly attenuated anxiety-like behaviors in both naïve animals and mice with inflammatory pain, while inhibition of these cells increased anxiety. Notably, activation of these neurons decreased heart rate and increased heart rate variability, suggesting that they reduce anxiety through modulation of the autonomic nervous system. Our study identifies ovBNSTGA/ovBNSTNtsr1neurons as one of the brain’s endogenous anxiolytic centers and a potential therapeutic target for treating anxiety-related disorders.

HIGHLIGHTS

General anesthetics and anxiolytics activate a population of neurons in the ovBNST

Anesthesia-activated ovBNST neurons bidirectionally modulate anxiety-like behavior

Most anesthesia-activated ovBNST neurons express neurotensin receptor 1

ovBNSTNtsr1neuron activation shifts autonomic responses to an anxiolytic state
Combinatorial microRNA activity is essential for the transition of pluripotent cells from proliferation into dormancy
Authors: Iyer Dhanur P. , Moyon Lambert , Ringeling Francisca R. , Cheng Chieh-Yu , Wittler Lars , Canzar Stefan , Marsico Annalisa , Bulut-Karslioglu Aydan
Published: December 2023

Dormancy is a key feature of stem cell function in adult tissues as well as embryonic cells in the context of diapause. The establishment of dormancy is an active process that involves extensive transcriptional, epigenetic, and metabolic rewiring1,2. How these processes are coordinated to successfully transition cells to the resting dormant state remains unclear. Here we show that microRNA activity, which is otherwise dispensable for pre-implantation development, is essential for the adaptation of early mouse embryos to the dormant state of diapause. In particular, the pluripotent epiblast depends on miRNA activity, the absence of which results in loss of pluripotent cells. Through integration of high-sensitivity small RNA expression profiling of individual embryos and protein expression of miRNA targets with public data of protein-protein interactions, we constructed the miRNA-mediated regulatory network of mouse early embryos specific to diapause. We find that individual miRNAs contribute to the combinatorial regulation by the network and the perturbation of the network compromises embryo survival in diapause. Without miRNAs, nuclear and cytoplasmic bodies show aberrant expression, concurrent with splicing defects. We identified the nutrient-sensitive transcription factor TFE3 as an upstream regulator of diapause-specific miRNAs, linking cytoplasmic mTOR activity to nuclear miRNA biogenesis. Our results place miRNAs as a critical regulatory layer for the molecular rewiring of early embryos to establish dormancy.