bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal Trends in Cardiac Rehabilitation Participation and Its Core Components
Authors: Vonk Thijs , Maessen Martijn F.H. , Hopman Maria T.E. , Snoek Johan A. , Aengevaeren Vincent L. , Franklin Barry A. , Eijsvogels Thijs M.H. , Bakker Esmee A.
Published: February 2024

Purpose:

Patient- and disease-specific data on cardiac rehabilitation (CR) participation and changes over time are limited. The objective of this study was to describe time trends in CR participation between 2013 and 2019 and provides insights into the utilization of CR components.

Methods:

Patients with cardiovascular disease (CVD) with an indication for CR were enrolled between 2013 and 2019. Dutch health insurance claims data were used to identify CR participation and its components.

Results:

In total, 106 212 patients with CVD were included of which 37% participated in CR. Participation significantly increased from 28% in 2013 to 41% in 2016 but remained unchanged thereafter. Participation was highest in the youngest age groups (<50 yrs 52%; 50-65 yrs 50%), men (48%), patients with ST-segment elevation myocardial infarction (73%), non–ST-segment elevation myocardial infarction (59%), and coronary artery bypass grafting (82%). In contrast, it was the lowest in the oldest age group (≥85 yrs 8%), women (30%), and in patients with heart failure (11%). Most participants in CR received referral plus an admission session (97%) and exercise training (82%), whereas complementary services related to dietary (14%) and mental health counseling (10%) had a low utilization.

Conclusions:

CR participation rates increased to 41% in 2016 but remained unchanged thereafter. Participation modulators included age, sex, CVD diagnosis, and undergoing a cardiothoracic procedure. Education and exercise sessions were frequently adopted, but dietary and mental health counseling had a low utilization rate. These findings suggest the need for reinvigorated referral and novel enrollment strategies in specific CVD subgroups to further promote CR participation and its associated underutilized adjunctive services.
Age-dependent association of central blood pressure with cardiovascular outcomes: a cohort study involving 34 289 participants using the UK biobank
Authors: Wang Shuqi , Wong Samuel Y.S. , Yip Benjamin H.K. , Lee Eric K.P.
Published: February 2024

Background:

It remained unclear whether central blood pressures (BP) was more closely associated with cardiovascular disease (CVD) than brachial BP in different age groups.

Objectives:

To investigate the age-stratified association of CVD with brachial and central BPs, and to evaluate corresponding improvement in model performance.

Methods:

This cohort study included 34 289 adults without baseline CVD from the UK Biobank dataset. Participants were categorized into middle-aged and older aged groups using the cut-off of age 65 years. The primary endpoint was a composite cardiovascular outcome consisting of cardiovascular mortality combined with nonfatal coronary events, heart failure and stroke. Multivariable-adjusted hazard ratios expressed CVD risks associated with BP increments of 10 mmHg. Akaike Information Criteria (AIC) was used for model comparisons.

Results:

In both groups, CVD events were associated with brachial or central SBP (P ≤ 0.002). Model fit was better for central SBP in middle-aged adults (AIC 4427.2 vs. 4429.5), but model fit was better for brachial SBP in older adults (AIC 10 246.7 vs. 10 247.1). Central SBP remained significantly associated to CVD events [hazard ratio = 1.05; 95% confidence interval (CI) 1.0–1.1] and improved model fit (AIC = 4426.6) after adjustment of brachial SBP only in the middle-aged adults. These results were consistent for pulse pressure (PP).

Conclusion:

In middle-aged adults, higher central BPs were associated with greater risks of CVD events, even after adjusting for brachial BP indexes. For older adults, the superiority of central BP was not observed. Additional trials with adequate follow-up time will confirm the role of central BP in estimating CVD risk for middle-aged individuals.
Sex differences in blood pressure phenotypes over time – the HELIUS study
Authors: Vriend Esther M.C. , Bouwmeester Thomas A. , Franco Oscar H. , Galenkamp Henrike , Zwinderman Aeilko H. , van den Born Bert-Jan H. , Collard Didier
Published: February 2024

Background:

Hypertension can be classified into different phenotypes according to systolic and diastolic blood pressure (BP). In younger adults, these phenotypical differences have different prognostic value for men and women. However, little is known about sex differences in the natural course of different BP phenotypes over time.

Methods:

We used baseline and follow-up data from the multiethnic, population-based HELIUS study to assess differences in BP phenotypes over time in men and women aged < 45 years stratified according to baseline office BP into normotension (<140/<90 mmHg), isolated systolic hypertension (ISH, ≥140/<90 mmHg), isolated diastolic hypertension (IDH, <140/≥90 mmHg) or systolic diastolic hypertension (SDH, ≥140/≥90 mmHg). Logistic regression adjusted for age, ethnicity, and follow-up time was used to assess the risk of hypertension at follow-up (BP ≥140/90 mmHg or use of antihypertensive medication), stratified by sex.

Results:

We included 4103 participants [mean age 33.5 years (SD 7.4), 43.4% men] with a median follow-up time of 6.2 years. Compared to normotensive individuals, the age-adjusted odds ratios (OR) for having hypertension at follow-up were 4.78 (95% CI 2.90; 7.76) for ISH, 6.02 (95% CI 3.70; 9.74) for IDH and 33.73 (95% CI 20.35; 58.38) for SDH in men, while in women, OR were 10.08 (95% CI 4.09; 25.56) for ISH, 27.59 (95% CI 14.68; 53.82) for IDH and 50.58 (95% CI 24.78; 114.84) for SDH.

Conclusions:

The risk of hypertension at follow-up was higher among women for all phenotypes compared to men, particularly in those with IDH. Findings of this study emphasize the importance of close BP monitoring in the young, especially in women.
Beyond the Surface: A Systematic Review of Perforating and Penetrating Globe Injuries From Blepharoplasty
Authors: Meyer Benjamin I. , Shoji Marissa K. , Zamani Kambiz A. , Bozung Alison K. , Lee Wendy W.
Published: February 2024

Purpose:

This study aims to address the infrequent but serious complication of globe injuries in blepharoplasty.

Methods:

A case series of 3 patients with globe injuries postblepharoplasty is presented, along with a systematic literature review that revealed 13 previously reported cases. Quantitative and comparative analysis is described.

Results:

Injuries ranged from deep thermal burns to full-thickness corneal or scleral lacerations, with one instance of traumatic cataract. The median time from surgery to symptom onset was 1 day, with a concerning median delay of 7 days to presentation to an ophthalmologist. Visual outcomes were generally poor, with nearly all patients experiencing permanent visual morbidity. The systematic review revealed 3 cases of endophthalmitis following perforating scleral injuries. Comparative analysis showed no significant differences in visual outcomes between penetrating and perforating injuries.

Conclusions:

The findings of this study emphasize the need for increased vigilance for globe injuries that require prompt ophthalmological evaluation following blepharoplasty, especially considering the observed delay in presentation and the extent of visual morbidity. The study advocates for improved practitioner training in recognizing and managing these complications and underscores the importance of patient education regarding the potential risks and the necessity of timely postoperative care.
Long-Term Outcome for Primary Papillomas of the Lacrimal Drainage System
Authors: Vahdani Kaveh , Rose Geoffrey E.
Published: February 2024

Purpose:

To report long-term outcomes after surgery for primary benign papillomas of the lacrimal drainage system.

Methods:

Retrospective review of patients with primary lacrimal drainage system papillomas, first seen between 1984 and 2021, but excluding lesions with sino-nasal origin or malignant histology. Patients were categorized by tumor histology (squamous, transitional, and mixed cell) and growth pattern (exophytic, endophytic, or mixed).

Results:

Thirty patients (18 female; 60%) presented at a mean age of 46.1 years (12–79 years). Over an average follow-up of 10.4 years, 30% of patients experienced recurrence, with rates differing slightly by growth pattern: 25% for exophytic tumors and 40% for endophytic and mixed-pattern tumors (p = 0.431). The overall 5-year recurrence-free survival was 67% (± 9% standard error), this being slightly higher for exophytic lesions (75% ± 10%) as compared to 48% (± 19%) for tumors with an endophytic component (p = 0.370). No cases of malignant transformation were observed, and the tumor type at recurrence matched the initial diagnosis.

Conclusion:

Primary benign papillomas of the lacrimal drainage system have a long-term recurrence rate of about one-third, with a higher frequency in those exhibiting an endophytic growth pattern. The study highlights the importance of prolonged surveillance for recurrence, especially for endophytic and mixed growth pattern tumors, and for the potential to undergo malignant transformation. The results support the effectiveness of endoscopic surgical excision or laser thermos-ablation in managing recurrent lacrimal drainage system papillomas after dacryocystorhinostomy.
Sinonasal Chondrosarcoma With Unusual Orbital Invasion
Authors: Pietris James , Tong Jessica Y. , Valentine Rowan , Nolan James , Selva Dinesh
Published: February 2024

A case is presented of a 43-year-old male with a chronic history of progressive nasal obstruction and epiphora. MRI confirmed a heterogeneous mass involving the middle and superior turbinates with T2 hyperintense and calcified components, with extension into the inferomedial orbit. Tissue biopsy revealed a grade 2 chondrosarcoma of the conventional subtype. Endonasal wide local resection of the lesion was performed with clear margins. The patient had no functional sequelae and will undergo routine surveillance.
Opioid Misuse Harm Reduction
Authors: Bailey Nancy R. , Mitchell Kimberly A. , Miller Theresa M.
Published: February 2024

Background/Aims

The misuse of opioids by the public is a major health issue. Prescription opioids and nonprescription opioids, such as heroin and opium, are misused in epidemic proportions. When opioids are used incorrectly or illegally, they can lead to drug dependence, addiction, morbidity, and mortality. This program is in collaboration with the Jolt Foundation that provides resources to prevent opioid overdose deaths.

Design/Methods

This program involves community education on the dangers of opioid use and training on the use of naloxone rescue procedures to prevent overdose deaths. A pretest–posttest design was employed to determine if participants gained knowledge regarding the naloxone administration procedures.

Participants

The researcher presented 10 community naloxone trainings that included staff from 20 different social service agencies, two schools, and three local churches. Each agency received at least one naloxone kit.

Findings

The outcomes were met and included educating 137 participants on the risk factors and signs and symptoms of opioid overdose and the proper procedure to administer naloxone. One hundred twenty-eight posttests were returned and showed that the objectives for the project were met. The overall mean score for the pretests was 65.00 (n = 126) with a standard deviation of 19.01, and the overall mean for the posttests was 86.64 (n = 128) with a standard deviation of 14.60.

Conclusions

Community social service agency staff were successfully educated to respond appropriately to overdose situations in a group training setting as evidenced by significant posttest scores.
Application of tele-neuropsychology and tele-mental health before and during COVID-19 era: a bibliometric analysis
Authors: Ali Abraish , Zafar Rameen , Kumar Kanwal Ashok , Shariq Kainat , Motiani Vanita , Ibrahim Sufyan , Farhat Hadi
Published: February 2024

Background:

Telehealth use was previously limited by strict regulations and financial constraints. However, the pandemic prompted some countries to ease their telehealth laws. Thus, we conducted a bibliometric analysis and network visualization to gauge changes in tele-neuropsychology (Tele-NP) and tele-mental Health (Tele-MH) trends with the onset of the COVID-19 pandemic.

Materials and methods:

The authors conducted a literature search on SCOPUS and included relevant articles pertaining to Tele-NP and Tele-MH, which were published before the COVID-19 pandemic (2017–2019) and during the COVID-19 pandemic (2020–2022). The authors presented publication patterns on psychiatric disorders, mode of administration, journals, active countries, authors, affiliations, funding sponsors, keywords, publication, and citation output.

Results:

Three hundred forty-one articles were included in our study with 80 articles before the pandemic and 261 during the pandemic. Our analysis revealed the greatest increase in publications and citations output was from the year 2020 to 2021. A greater number of journals published tele-NP and tele-MH-related research, with higher frequency, during the COVID-19 pandemic with Telemedicine and E-health leading the way. WHO regional analysis revealed that the Region of the Americas (AMRO) was the leading contributor in terms of publications. Harvard Medical Center remained the number one contributor both before and during the COVID-19- pandemic. Publications by funding sponsors, particularly by those that were US-based, increased twice as much during the pandemic.

Conclusion:

The increase in research output following the COVID-19 outbreak reflects the growing interest and relevance of telemedicine for the delivery of mental health services.
HIV Infection Modifies the Role of Prior Treponema pallidum Infection in the Clinical Presentation of Early Syphilis Among Adult Patients From Sexually Transmitted Infection Clinics in Peru
Authors: Reyes-Diaz Michael , Malca Joselito , Konda Kelika A. , Vargas Silver K. , Calvo Gino M. , Caceres Carlos F. , Klausner Jeffrey D.
Published: February 2024

Background

We aimed to compare the clinical presentations (symptomatic vs. asymptomatic) with prior Treponema pallidum infection status (first infection vs. reinfection) among people with early syphilis.

Methods

We used data from PICASSO, a cohort study in Peru that enrolled people with active syphilis from May 2019 to August 2021. Study participants had early syphilis and a prior syphilis serological test result within the prior 12 months to determine prior T. pallidum infection status. We calculated prevalence ratios (PRs) of symptomatic clinical presentation (primary or secondary syphilis) by prior T. pallidum infection status, stratified by HIV infection status. In addition, we explored the association of prior T. pallidum infection status and lesion presentation, stratified by primary and secondary syphilis cases, using the Fisher exact test.

Results

We include 84 T. pallidum reinfection cases and 61 first infection cases. We found increased frequency of symptomatic clinical presentation among first-infection cases (39% vs. 20%; PR, 1.94; P = 0.014). This association was stronger among persons living without HIV infection (38% vs. 7%; adjusted PR, 6.63; P = 0.001) in comparison to those living with HIV infection (45% vs. 34%; adjusted PR, 1.38; P = 0.458). Among secondary syphilis cases, more participants from the reinfection group reported that their lesions improved 1 week after treatment (100% vs. 29%, P = 0.045) compared with those with a first infection. Among the primary syphilis cases, all participants reported that their lesions improved 1 week after treatment.

Conclusions

Prior syphilis was associated with a decreased prevalence of symptomatic reinfection, especially among persons not living with HIV infection.
Pan-cancer Genomic Analysis of AXL Mutations Reveals a Novel, Recurrent, Functionally Activating AXL W451C Alteration Specific to Myxofibrosarcoma
Authors: Williams Erik A. , Vegas Isabella , El-Senduny Fardous F. , Zhang Jessica , Mata Douglas A. , Hiemenz Matthew C. , Hughes Sarah R. , Sa Brianna C. , Kraft Garrett P. , Gorbatov Nicole , Foley-Peres Kathleen , Sanchez Edward Z. , Milikowski Clara , Williams Kevin Jon , Ross Jeffrey S. , Kurzrock Razelle , Montgomery Elizabeth A. , Lombard David B. , Kumar Surinder
Published: February 2024

Myxofibrosarcoma (MFS) is a common soft tissue sarcoma of the elderly that typically shows low tumor mutational burden, with mutations in TP53 and in genes associated with cell cycle checkpoints (RB1, CDKN2A). Unfortunately, no alterations or markers specific to MFS have been identified and, as a consequence, there are no effective targeted therapies. The receptor tyrosine kinase AXL, which drives cellular proliferation, is targetable by new antibody-based therapeutics. Expression of AXL messenger RNA is elevated in a variety of sarcoma types, with the highest levels reported in MFS, but the pathogenic significance of this finding remains unknown. To assess a role for AXL abnormalities in MFS, we undertook a search for AXL genomic alterations in a comprehensive genomic profiling database of 463,546 unique tumors (including 19,879 sarcomas, of which 315 were MFS) interrogated by targeted next-generation DNA and/or RNA sequencing. Notably, the only genomic alterations recurrent in a specific sarcoma subtype were AXL W451C (n = 8) and AXL W450C (n = 2) mutations. The tumors involved predominantly older adults (age: 44 to 81 [median: 72] y) and histologically showed epithelioid and spindle-shaped cells in a variably myxoid stroma, with 6 cases diagnosed as MFS, 3 as undifferentiated pleomorphic sarcoma (UPS), and 1 as low-grade sarcoma. The AXL W451C mutation was not identified in any non-sarcoma malignancy. A review of publicly available data sets revealed a single AXL W451C-mutant case of UPS that clustered with MFS/UPS by methylation profiling. Functional studies revealed a novel activation mechanism: the W451C mutation causes abnormal unregulated dimerization of the AXL receptor tyrosine kinase through disulfide bond formation between pairs of mutant proteins expressing ectopic cysteine residues. This dimerization triggers AXL autophosphorylation and activation of downstream ERK signaling. We further report sarcomas of diverse histologic subtypes with AXL gene amplifications, with the highest frequency of amplification identified in MFS cases without the W451C mutation. In summary, the activating AXL W451C mutation appears highly specific to MFS, with a novel mechanism to drive unregulated signaling. Moreover, AXL gene amplifications and messenger RNA overexpression are far more frequent in MFS than in other sarcoma subtypes. We conclude that these aberrations in AXL are distinct features of MFS and may aid diagnosis, as well as the selection of available targeted therapies.
Excessive Use of Benzodiazepines Is a Risk Factor for Endotracheal Intubation in Children Who Present to Emergency With Prehospital Status Epilepticus
Authors: Han Velda X. , Goh Kee Hang , Boi Yu Shan , Lin Jeremy B. , Wang Furene S. , Lin Diana Y. , Kao Pao Tang
Published: February 2024

Objectives

There is lack of evidence-based information on the use and timing of endotracheal intubation (ETI) in children with prehospital status epilepticus (SE).

Methods

The aim of this study was to investigate ETI use, timing, risk factors, and outcomes in children presenting to a single-center children's emergency (CE) with prehospital SE, over a 5-year period.

Results

A total of 118 events involving children presenting to CE with ongoing prehospital SE were included, and 39% (46/118) of the events required ETI. The most common indication for ETI was respiratory depression. The median time to intubation after arrival at CE was 20.0 minutes (1–155 minutes). Risk factors associated with ETI use include the administration of more than 2 benzodiazepines (26.1% vs 4.2%, P < 0.001) and the use of second- or third-line antiepileptic therapy (P < 0.001). The use of more than 2 doses of benzodiazepines was found in 12.7% (15/118) of the patients. In patients who received excessive benzodiazepines, 87% (13/15) of them required intubation.

Conclusions

Excessive use of benzodiazepine was found to be a main risk factor for ETI in patients with prehospital SE. Avoidance of the excessive use of benzodiazepines and adhering to clinical management guidelines may reduce the risk for ETI in the CE. The best approach to airway management in children with prehospital SE is lacking and urgently needed.
Medication Management Strategies by Community-Dwelling Older Adults: A Multisite Qualitative Analysis
Authors: Jallow Fatoumata , Stehling Elisa , Sajwani-Merchant Zara , Daniel Kathryn M. , Fulda Kimberly G. , Gurses Ayse P. , Arbaje Alicia I. , Xiao Yan
Published: February 2024

Objectives

Community-dwelling older adults taking 5 or more medications are at risk for medication-related harm. Managing multiple medications is a challenging task for patients and caregivers. Community-dwelling older adults self-manage their medications with minimal healthcare professional supervision. Although organizations, such as the Food and Drug Administration, often issue guidelines to ensure medication safety, how older adults understand and mitigate the risk of harm from medication use in the home environment is poorly understood.

Methods

We conducted semistructured interviews with community-dwelling older adults 65 years and older who took 5 or more prescription medications to explore medication safety strategies they use. We also compared 2 organizations’ medication safety guidelines for areas of concordance and discordance.

Results

A total of 28 older adults were interviewed. Four overarching themes of medication management strategies emerged: collaborating with prescribers, collaborating with pharmacists, learning about medications, and safe practices at home. Study findings revealed that older adults followed some of the published guidelines by the 2 government organizations, although there were some areas of discord. Some of the strategies used were unintentionally against the recommended guidelines. For example, older adults tried weaning themselves off their medications without notifying their providers.

Conclusions

Older adults and their caregivers in our study used strategies different from those recommended by government organizations in managing medications to enhance drug safety. Patient-provider collaboration and positive patient outcomes can be improved by understanding and respecting strategies older adults use at home. Future studies must effectively incorporate older adults’ perspectives when developing medication safety guidelines.
A Prospective Quasi-Experimental Study of Multifaceted Interventions Including Computerized Drug Utilization Evaluation to Improve an Antibiotic Stewardship Program
Authors: Suksamai Sunudtha , Sajak Sirinporn , Thongphubeth Kanokporn , Khawcharoenporn Thana
Published: February 2024

Objective

This study aimed to determine and evaluate interventions that improve an antibiotic stewardship program (ASP) in reduction of the amount of antibiotic use and errors in drug utilization evaluation (DUE) form completion.

Methods

A prospective quasi-experimental study was conducted to evaluate the effectiveness of the multifaceted interventions (preauthorization with computerized DUE, self-supervised checklists, and short active reminders of the antibiotic guidelines recommendations) incorporating an ASP among hospitalized internal medicine patients in a Thai tertiary care center. The preintervention period was from January to December 2018, and the postintervention period was from February 2019 to January 2020.

Results

A total of 9188 and 9787 patient data were analyzed during the preintervention and postintervention periods, respectively. The overall median antibiotic use (defined daily dose/1000 bed-days) was significantly decreased in the postintervention period compared with the preintervention period (867.68 versus 732.33; P < 0.001). The reduction in antibiotic use was predominantly observed among broad-spectrum antibiotics, including cefoperazone/sulbactam (15.35 versus 9.75; P = 0.04), cefepime (13.09 versus 6.37; P = 0.003), ciprofloxacin (32.99 versus 17.83; P < 0.001), piperacillin/tazobactam (99.23 versus 91.93; P = 0.03), meropenem (2.01 versus 0.99; P < 0.001), imipenem/cilastatin (9.53 versus 4.59; P = 0.04), and colistin (74.70 versus 22.34; P < 0.0001). The overall rate of errors in DUE form completion was significantly decreased after the intervention (40% versus 28%; P < 0.001). The incidence of carbapenem-resistant Enterobacteriaceae infections/colonization was significantly lower in the postintervention period (0.27 versus 0.12/1000 bed-days; P = 0.02).

Conclusions

The study multifaceted interventions incorporating ASP were associated with significant reduction in the amount of broad-spectrum antibiotic use, DUE form completion errors, and incidence of carbapenem-resistant Enterobacteriaceae infection/colonization.
Effectiveness of Postoperative Single-shot and Continuous Transverse Abdominis Plane Block Compared to Conventional Analgesia in Hand-assisted Laparoscopic Live-donor Nephrectomy
Authors: De Leon Fransia , Alghannam Karima , Gul Hadia Lala , Goussous Naeem , Mineyev Neal , Than Peter A. , Perez Richard V. , Sageshima Junichiro
Published: February 2024

Background.

Few studies have evaluated the efficacy of transverse abdominis plane (TAP) block in patients undergoing hand-assisted laparoscopic live-donor nephrectomy (HALN). We aimed to evaluate the analgesic effectiveness of TAP block as part of a multimodal pain management regimen in patients undergoing HALN.

Methods.

We retrospectively reviewed the medical records of living kidney donors at our center between June 2016 and February 2020. HALNs were performed via a transperitoneal approach through a suprapubic incision. Additional laparoscopic ports were used in the upper midabdomen. In consenting donors, TAP block was performed postoperatively under ultrasound guidance with either a single-shot or continuous infusion of long-acting local anesthetic (0.2%–0.5% ropivacaine). All the patients received postoperative around-the-clock ketorolac and acetaminophen.

Results.

Overall, 72 donors received the block (block group, 38 single-shot, 34 continuous), whereas 86 donors did not receive the block (control group). Baseline characteristics were comparable between the groups except for body weight (control: 71.8 ± 13.3 versus block: 77.8 ± 17.3 kg; P = 0.01) and intraoperative opioid dose (32.1 ± 9.6 versus 26.6 ± 10.7 morphine milligram equivalents; P < 0.001). After adjusting for baseline differences, postoperative opioid requirements were similar between the groups. When the baseline pain scale was adjusted for, there was no difference in the overall pain scale scores between the groups (P = 0.242). Subgroup analyses comparing single-shot or continuous TAP versus control did not show any differences.

Conclusions.

With the caveat of the retrospective nature of the study, the adjunctive effect of TAP block after transabdominal HALN was limited when other multimodal analgesia was used.
Distinct Changes in Gut Microbiota of Patients With Kidney Graft Rejection
Authors: Visconti Vanessa , Wirtz Stefan , Schiffer Mario , Müller-Deile Janina
Published: February 2024

Background.

Kidney graft rejection still represents the major cause of graft loss in kidney transplant recipients. Of growing interest is the bidirectional relationship between gut microbiome and immune system suggesting that gut microbiota can affect allograft outcome.

Methods.

In this cross-sectional case-control study, we characterized the gut microbial profile of adult renal transplant recipients with and without graft rejection to define a cohort-specific microbial fingerprint through 16S ribosomal RNA gene sequencing. We used very strict inclusion and exclusion criteria to address confounder of microbiota composition.

Results.

Different relative abundances in several gut microbial taxa were detectable in control patients compared with patients with kidney allograft rejection. Alpha diversity was lower in the rejection group and beta diversity revealed dissimilarity between patients with and without kidney graft rejection (P < 0.01). When the rejection group was stratified according to different types of allograft rejection, major changes were identified between patients with chronic T-cellular–mediated rejection and controls. Changes in alpha diversity within the gut microbiome were related to the probability of chronic T-cellular–mediated rejection (P < 0.05). Kidney transplant patients without rejection showed significant enrichment of rather anti-inflammatory taxa whereas in the rejection group bacteria well known for their role in chronic inflammation were increased. For example, amplicon sequence variant (ASV) 362 belonging to the genus Bacteroides and ASV 312 belonging to Tannerellaceae were enriched in no rejection (P < 0.001 and P < 0.01), whereas ASV 365 was enriched in patients with allograft rejection (P = 0.04). Looking at metagenomic functions, a higher abundance of genes coding for enzymes involved in bacterial multidrug resistance and processing of short-chain fatty acids was found in patients without rejection but an increase in enzymes involved in nicotinamide adenine dinucleotide phosphate production was seen in patients with allograft rejection.

Conclusions.

A distinct microbial fingerprint of patients with allograft rejection might serve as noninvasive biomarker in the future.
Vagus Nerve Stimulation as an Alternative to Maintenance Electroconvulsive Therapy for Difficult-to-Treat Depression
Authors: Migchels Charlotte , Obbels Jasmien , McAllister-Williams Hamish , Demyttenaere Koen , Sienaert Pascal
Published: February 2024

Vagus nerve stimulation (VNS), an implantable neurostimulator, provides a valuable long-term treatment option for patients with difficult-to-treat depression. It has been reported that previous response to electroconvulsive therapy (ECT) might predict a better response to VNS and that VNS could reduce or eliminate the need for maintenance ECT in some patients. We present the case of a patient who received a total of more than 120 sessions of ECT over the course of 13 years because of a major depressive disorder, with favorable response but without achieving full remission. After implantation of VNS, ECT was discontinued, and her depressive symptoms improved, achieving remission within 12 months. This case supports VNS as an alternative to maintenance ECT in patients with difficult-to-treat depression who have shown previous response to ECT treatment.
Retromer-dependent lysosomal stress in Parkinson's disease
Authors: Alessi Dario R. , Cullen Peter J. , Cookson Mark , Merchant Kalpana M. , Small Scott A.
Published: February 2024

While causative mutations in complex disorders are rare, they can be used to extract a biological pathway whose pathogenicity can generalize to common forms of the disease. Here we begin by relying on the biological consequences of mutations in LRRK2 and VPS35, genetic causes of autosomal-dominant Parkinson's disease, to hypothesize that ‘Retromer-dependent lysosomal stress’ represents a pathway that can generalize to idiopathic Parkinson's disease. Next, we outline a series of studies that can test this hypothesis, including the development of biomarkers of pathway dysfunction. If validated, the hypothesis can suggest a unified mechanism of disease and might inform future diagnostic and therapeutic investigations.

This article is part of a discussion meeting issue ‘Understanding the endo-lysosomal network in neurodegeneration’.
Preference for Social Motion in Autistic Adults
Authors: Matyjek Magdalena , Bast Nico , Soto Faraco Salvador
Published: February 2024

Autism is often linked to attenuated social attention, including a lowered looking preference to biological motion in autistic compared to non-autistic children. This looking preference has been suggested as an autism marker in childhood. However, few studies have investigated whether this bias persists into adulthood. Furthermore, the underlying cognitive mechanism of this group difference is largely unknown. Pupillary responses have been established as an index of salience processing and are thus a promising measurement of the cognitive bases of looking preference. The present study examined differences in looking preference and pupillary responses to social versus geometric motion between autistic and non-autistic adults (N=66). In terms of preference, autistic adults demonstrated a reduced spontaneous looking toward social stimuli compared to the non-autistic group. Whereas the former displayed no clear preference for either motion type, the latter showed a strong preference for social motion. In terms of pupillary responses, the autistic group showed faster and larger pupil dilation for social motion compared to the non-autistic group, consistent with heightened cognitive effort. These results suggest persistent differences in social attention across the developmental lifespan in autism.
Outcome evaluation of effect of organizational strategies on reduction of patient waiting time at the outpatient department at Kilimanjaro Christian Medical Centre – Northern, Tanzania
Authors: Mollel Henry , Mwanswila Manasseh Joel
Published: February 2024

Background The Tanzanian healthcare system has long grappled with extended waiting times in outpatient departments (OPD). Studies at Kilimanjaro Christian Medical Centre (KCMC) revealed an average wait of six hours, marking KCMC with the longest waiting time among Tanzanian referral hospitals. Thus, this study was undertaken to assess the efficacy of the programme interventions and their effect on waiting time at KCMC, OPD. Methods An analytical cross-sectional approach quantitatively and qualitatively examined the subject. The study enrolled 412 patients who completed structured questionnaires, while 14 participants underwent in-depth interviews (ID) (8 healthcare providers, 6 patients) from 3rd to 14th, 2023. Documentary review supplemented data. Quantitative analysis included descriptive statistics, bivariable, and multivariable techniques. Qualitative data underwent thematic analysis. Significance tests were at a 5% level. Result The overall OPD waiting time significantly decreased to 3.30 hours IQR (2.51-4.08) in contrast to the previous 6 hours prior to the intervention, showing the effectiveness of the intervention achieving a reduction of waiting time by 55%. Improvements were particularly evident, waiting time for registration (9 minutes), payments (10 minutes), triage (14 minutes for patients with insurance) and pharmacy (4 minutes). The implementation of Ushers emerged as a significant predictor to patient waiting time (AOR = 2.08, 95% CI, 1.10-3.94, p-value=0.025). Based on the IDI, the findings indicate a favourable change in patients' attitudes towards waiting time at the OPD. However, there is skepticism regarding the expansion of hospital infrastructure and its effect on waiting time, as well as reliance on auxiliary support due to insufficient human resources. Conclusion Even though the established intervention strategies have managed to reduce waiting time, additional measures to attain the global standard of waiting time from 30 minutes to 2 hours are needed.
The Body Knows Better: Sensorimotor signals reveal "Suboptimal" inference of the Sense of Agency in the human mind
Authors: Applebaum Asaf , Netzer Ophir , Stern Yonatan , Zvilichovsky Yair , Mashiah Oz , Salomon Roy
Published: February 2024

Sense of Agency (SoA) is the feeling of control over our actions. SoA has been suggested to arise from both implicit sensorimotor integration as well as higher-level decision processes. SoA is typically measured by collecting participants' subjective judgments, conflating both implicit and explicit processing. Consequently, the interplay between implicit sensorimotor processing and explicit agency judgments is not well understood. Here, we evaluated in one exploratory and one preregistered experiment (N=60), using a machine learning approach, the relation between a well-known mechanism of implicit sensorimotor adaptation and explicit SoA judgments. Specifically, we examined whether subjective judgments of SoA and sensorimotor conflicts could be inferred from hand kinematics in a sensorimotor task using a virtual hand (VH). In both experiments participants performed a hand movement and viewed a virtual hand making a movement that could either be synchronous with their action or include a parametric temporal delay. After each movement, participants judged whether their actual movement was congruent with the movement they observed. Our results demonstrated that sensorimotor conflicts could be inferred from implicit motor kinematics on a trial by trial basis. Moreover, detection of sensorimotor conflicts from machine learning models of kinematic data provided more accurate classification of sensorimotor congruence than participants' explicit judgments. These results were replicated in a second, preregistered, experiment. These findings show evidence of diverging implicit and explicit processing for SoA and suggest that the brain holds high-quality information on sensorimotor conflicts that is not fully utilized in the inference of conscious agency.
Marsilea: An intuitive generalized visualization paradigm for complex datasets
Authors: Zheng Yimin , Zheng Zhihang , Rendeiro André F. , Cheung Edwin
Published: February 2024

Contemporary data visualization is challenged by the growing complexity and size of datasets, often comprising numerous interrelated features. Traditional visualization methods struggle to capture these complex relationships fully or are specialized to a domain requiring familiarity with multiple visualization tools. We introduce a novel and intuitive general visualization paradigm, termed “cross-layout visualization”, which integrates multiple plot types in a cross-like structure. This paradigm allows for a central main plot surrounded by secondary plots, each capable of layering additional features for enhanced context and understanding. To operationalize this paradigm, we present “Marsilea”, a Python library designed for creating complex visualizations with ease. Marsilea is notable for its modularity, diverse plot types, compatibility with various data formats, and is available in a coding-free web-based interface for users of all experience levels. We showcase its versatility and broad applicability by re-creating existing visualizations and creating novel visualizations that include elements such as heatmaps, sequence motifs, and set intersections that are typically beyond the scope of existing general visualization tools. The cross-layout paradigm, exemplified by Marsilea, offers a flexible, customizable, and intuitive approach to complex data visualization, promising to enhance data analysis across scientific domains.
Atox1-Cyclin D1 Loop Activity is Critical for Survival of Tumor Cells with Inactivated TP53
Authors: Kuchur Oleg A. , Pogodaeva Sofya S. , Shcherbakova Anna V. , Tsymbal Sergey A.
Published: February 2024

The search for relevant molecular targets is one of the main tasks of modern tumor chemotherapy. To successfully achieve this, it is necessary to have the most complete understanding of the functioning of the cell's transcriptional apparatus, particularly related to proliferation. The p53 protein plays an important role in regulating processes such as apoptosis, repair, and cell division, and the loss of its functionality often accompanies various types of tumors and contributes to the development of chemoresistance. Additionally, the proliferative activity of tumor cells is closely related to the metabolism of transition metals. For example, the metallochaperone Atox1, a copper transporter protein, acts as a transcription activator for cyclin D1, promoting progression through the G1/S phase of the cell cycle. On the other hand, p53 suppresses cyclin D1 at the transcriptional level, thereby these proteins have divergent effects on cell cycle progression. However, the contribution of the interaction between these proteins to cell survival is poorly understood. This work demonstrates that there not only exists a positive feedback loop between Atox1 and cyclin D1, but also that the activity of this loop depends on the status of the TP53 gene. Upon inactivation of TP53 in A549 and HepG2 cell lines, the expression of ATOX1 and CCND1 genes is enhanced, and their suppression in these cells leads to pronounced apoptosis. This fundamental observation may be useful in selecting more precise interventions for combined therapy of p53-negative tumors.
Effects of sodium butyrate and rosemary leaves on performance, biochemical parameters, immune status, and carcass traits of broiler chickens
Authors: Shalaby Mostafa Abbas , Saifan Hamed Yahya , Abo-El-Sooud Khaled , Tony Mohamed Ahmed , Yassin Aya Mohye
Published: February 2024

ABSTRACT Effects of sodium butyrate (SB) and rosemary leaves (RL) on growth performance, biochemical profile, immune status, and carcass traits of broiler were evaluated. Fifty-one-day old Hubbard chicks (unsexed) were purchased from Al-Ahram Company for Poultry, Egypt and reared on floor pens in a private farm. The chicks were weighed on arrival and assigned at random into five equal groups, with four replicates each (25 chicks/replicate). Group 1 was fed on a broiler diet without any additions and used as a control. The diets of groups 2 and 3 were supplemented with 500 g/ton SB and 4 kg/ton RL, respectively. In group 4, the diet was enriched with 250g/ton SB plus 2 kg/ton RL. Chicks in group 5 were fed on a diet fortified with 500 g/ton SB plus 4 kg/ton RL. Body weight gain (BWG) and feed efficiency ratio (FER) were determined weekly. Biochemical indexes, immune system function, and carcass traits were determined. The results revealed that supplementing broiler diet with 500g/ton SB plus 4 kg/ton RL increased BWG and FER of birds. This diet decreased serum levels of aspartate aminotransferase, (AST) alanine aminotransferase (ALT), total cholesterol (TC), triglycerides (TG), malondialdehyde (MDA and increased superoxide dismutase (SOD), catalase (CAT), and immunoglobulins. It also boosted immunity as it elevated phagocytic activity, phagocytic index, lysozyme activity, and nitric oxide (NO) concentrations. Antibody titers against Newcastle disease virus were elevated. It can be concluded that supplementing broiler diet with 500g/ton SB plus 4 kg/ton RL improve performance, normalize biochemical profile, and boost immunity.
Transgenesis enables mapping of segmental ganglia in the leech Helobdella austinensis
Authors: Kuo Dian-Han , Szczupak Lidia , Weisblat David , Portiansky Enrique , Winchell Christopher , Lee Jun-Ru , Tsai Fu-Yu
Published: February 2024

The analysis of how neural circuits function in individuals and change during evolution is simplified by the existence of neurons identified as homologous within and across species. Invertebrates, including leeches, have been used for these purposes in part because their nervous systems comprise a high proportion of identified neurons, but technical limitations make it challenging to assess the full extent to which assumptions of stereotypy hold true. Here, we introduce Minos plasmid-mediated transgenesis as a tool for introducing transgenes into the embryos of the leech Helobdella austinensis (Spiralia; Lophotrochozoa; Annelida; Clitellata; Hirudinida; Glossiphoniidae). We identified an enhancer driving pan-neuronal expression of markers, including histone2B:mCherry, which allowed us to enumerate neurons in segmental ganglia. Unexpectedly, we find that adult Helobdella ganglia contain fewer and more variable numbers of neurons than in previously examined leech species.
Resistify - A rapid and accurate annotation tool to identify NLRs and study their genomic organisation
Authors: Smith Moray , Jones John T. , Hein Ingo
Published: February 2024

Background

Nucleotide-binding domain Leucine-rich Repeat (NLR) proteins are a key component of the plant innate immune system. In plant genomes NLRs exhibit considerable presence/absence variation and sequence diversity. Recent advances in sequencing technologies have made the generation of high-quality novel plant genome assemblies considerably more straightforward. Accurately identifying NLRs from these genomes is a prerequisite for improving our understanding of NLRs and identifying potential novel sources of disease resistance.

Results

Whilst several tools have been developed to predict NLRs, they are hampered by low accuracy, speed, and availability. Here, the NLR annotation tool Resistify is presented. Resistify is an easy-to-use, rapid, and accurate tool to identify and classify NLRs from protein sequences. Applying Resistify to the RefPlantNLR database demonstrates that it can correctly identify NLRs from a diverse range of species. Applying Resistify in combination with tools to identify transposable elements to a panel of Solanaceae genomes reveals a previously undescribed association between NLRs and Helitron transposable elements.

Conclusion

Resistify can rapidly identify NLRs within plant genomes and provides accurate structural classifications. Its ease of use and accessibility allows easy integration into bioinformatic workflows and projects, enhancing the study of this important group of genes. Applying Resistify to aSolanaceaepangenome reveals an undescribed association between NLRs and transposable elements.

Availability:https://github.com/SwiftSeal/resistify
Brainwide mesoscale functional networks revealed by focal infrared neural stimulation of the amygdala
Authors: Ping An , Wang Jianbao , García-Cabezas Miguel Ángel , Li Lihui , Zhang Jianmin , Gothard Katalin M. , Zhu Junming , Roe Anna Wang
Published: February 2024

The primate amygdala serves to evaluate emotional content of sensory inputs and modulate emotional and social behaviors; it modulates cognitive, multisensory and autonomic circuits predominantly via the basal (BA), lateral (LA), and central (CeA) nuclei, respectively. Based on recent electrophysiological evidence suggesting mesoscale (millimeters-scale) nature of intra-amygdala functional organization, we have investigated the connectivity of these nuclei using Infrared Neural Stimulation of single mesoscale sites coupled with mapping in ultrahigh field 7T functional Magnetic Resonance Imaging (INS-fMRI). Stimulation of multiple sites within amygdala of single individuals evoked ‘mesoscale functional connectivity maps’, allowing comparison of BA, LA and CeA connected brainwide networks. This revealed a mesoscale nature of connected sites, complementary spatial patterns of functional connectivity, and topographic relationships of nucleus-specific connections. Our data reveal a functional architecture of systematically organized brainwide networks mediating sensory, cognitive, and autonomic influences from the amygdala.