bluuebunny/crossref_metadata_2025 huggingface dataset:
Target Artery Outcomes Following Endovascular versus Open Surgical Repair of Thoracoabdominal Aortic Aneurysms – A Single Center Comparative Study
Authors: Huang Ying , Colglazier Jill , Mendes Bernardo C. , Pochettino Alberto , Kalra Manju , Greason Kevin L. , Tenorio Emanuel R. , Harmsen William S. , Oderich Gustavo S.
Published: November 2024

Objective:

To compare target artery (TA) outcomes after fenestrated or branched endovascular aortic repair (FB-EVAR) versus open surgical repair (OSR) of thoracoabdominal aortic aneurysms (TAAAs).

Background:

Few studies have compared TA outcomes after endovascular incorporation and open reconstruction.

Methods:

Among consecutive patients who underwent elective OSR or FB-EVAR of TAAAs (2008-2020), we reviewed those who had postoperative imaging studies evaluating TA. Data of FB-EVAR patients were obtained from a prospectively maintained institutional database. TAs included celiac, superior mesenteric, right and left renal arteries treated during TAAA repairs. Primary endpoint was TA patency (primary and secondary).

Results:

There were 131 patients (487 TAs) treated by OSR and 350 (1,300 TAs) by FB-EVAR. In the OSR group, 440 TAs (90.3%) were reconstructed by bypasses, and 47 (9.7%) by reimplantation. In the FB-EVAR group, 841 TAs (64.7%) were incorporated by fenestrations, and 459 (35.3%) by DBs. Thirty-day TA primary patency rates were not significantly different between FB-EVAR and OSR (99.4%% vs. 99.0%, P=0.36), but secondary patency rate was higher after FB-EVAR (99.8% vs. 99.0%, P=0.02). Three-year primary patency rates were 95.9% (95% confidence interval [CI], 94.7-97.2%) and 94.7% (95% CI, 92.2-97.2%), respectively; secondary patency rates were 98.5% (95% CI, 97.7-99.2%) and 94.7% (95% CI, 95.7-99.2%), respectively. There were no significant differences in late primary patency and secondary patency between groups (each P<0.05).

Conclusion:

Target artery primary and secondary patency rates following elective OSR or FB-EVAR were high. Endovascular repair was not associated with loss of primary patency and late secondary patency.
Too Big to Fail
Authors: Fuchs Juri , Rabaux-Eygasier Lucas , Husson Thomas , Fouquet Virginie , Guerin Florent , Hery Geraldine , Branchereau Sophie
Published: November 2024

Objective:

To assess the incidence of posthepatectomy liver failure (PHLF) and the role of the future liver remnant (FLR) in children undergoing major hepatectomy

Background:

Incidence and risk factors of PHLF in children are unclear, with no validated definition for this age group. Consequently, the role of the FLR in pediatric hepatectomy and evidence-based preoperative guidelines remains undefined.

Methods:

All pediatric patients undergoing major hepatectomy at a tertiary care center over a 10-year study period were analyzed. Preoperative imaging was used for volumetry. The incidence of PHLF was assessed by applying predefined definitions, and the prognostic impact of the FLR on PHLF and complications was evaluated.

Results:

A total of 125 children underwent major hepatectomy, including 35 trisectionectomies. There was a strong correlation between imaging-based measured total liver volume (TLV) and calculated standard liver volume (r = 0.728, P < 0.001). The median TLV-to-body weight (BW) ratio was 3.4%, and the median FLR/BW ratio was 1.5%. The median FLR-to-TLV ratio was 44% (range: 18%–97%). No clinically relevant PHLF occurred. FLR/TLV and FLR/BW ratios had low predictive value for postoperative liver dysfunction and morbidity.

Conclusions:

This is the largest reported single-center series of pediatric major hepatectomies. PHLF is exceedingly rare in children. The liver volume-to-BW ratio is higher in children compared with adults, and the FLR is sufficient even in extreme resections with <20% of the liver remnant. These findings strongly question the use of asociating liver partition and portal vein ligation for staged hepatectomy, portal vein embolization, or transplantation based on suspected insufficient liver remnants in children.
Brain MRI Lesions in Alexia Without Agraphia: A Case–Control Study
Authors: Shapiro Jeremy N. , Sharma Aseem , Trobe Jonathan D. , Walsh Ryan D. , Khanna Sangeeta
Published: November 2024

Background:

Alexia without agraphia (AWA) is an acquired reading disturbance associated with left posterior cerebral artery (PCA) infarction. Based on autopsy and neuroimaging, there are two explanations for its pathogenesis: a visual cortex–language cortex disconnection and a visual word-form agnosia. Our goal was to discover if more refined brain imaging in a case–control study would provide further imaging support for either of these hypotheses.

Methods:

A neuroradiologist masked to the presence of AWA reviewed diffusion-weighted and fluid-attenuated inversion recovery brain MRIs in patients who had left PCA infarctions with AWA (9 patients) or without AWA (18 patients) to characterize lesions in the splenium, left forceps major, and left fusiform gyrus.

Results:

Patients with AWA had various combinations of lesions in the splenium, left forceps major, and left fusiform gyrus. One of these regions was involved in 3 patients, 2 were involved in 3 patients, and 3 were involved in 3 patients. Most (89%) patients without AWA lacked involvement of any of these 3 regions.

Conclusions:

Our data provide imaging evidence for the two existing hypotheses of AWA. Involvement of any of these lesions on MRI imaging should encourage clinicians to obtain further neuropsychological testing.
Individual on Death Row Receiving Electroconvulsive Therapy (ECT) for Catatonia
Authors: Basden Brian J. , Surya Sandarsh , Rosenquist Peter B. , McCall William V.
Published: November 2024

Electroconvulsive therapy (ECT) is underused, logistically challenging for those who are justice-involved, and laced with ethical problems for those on death row. Herein we describe a case of a man without history of long-standing psychiatric illness who, after more than 15 years on death row, was hospitalized for altered mental status. After medical stabilization, the altered mental status persisted. On exam, he displayed signs of catatonic stupor with repetitive non–goal-directed motor activity, repetition of words, rigidity, and negativism, among others. The Bush-Francis Catatonia Rating Scale was found to be 23. Lorazepam was nontherapeutic. Hospital psychiatry considered ECT. Hospital medicine, medical prison staff, and the hospital ethics committee were consulted. Consent to treat catatonia with ECT was obtained from next of kin. Before treatment, the ECT psychiatrist spoke with prison staff regarding the presence of plastic restraints. To balance the competing demands of carceral policies and musculoskeletal protection, we implemented the practice of removing plastic restraints after the patient was sedated by anesthetic, with restraints being reapplied after the motor convulsion ended. Five days after 7 ECT treatments given thrice weekly, the catatonic symptoms remitted. Ethically, psychiatrists are not to restore competency for the purpose of execution. In this case, ECT was used by psychiatrists unaffiliated with the criminal legal system to reduce suffering and improve quality of life given the potentially fatal consequences of catatonia.
Elevated Blood Glucose in COVID-19 Patients: An explorative Study
Authors: Bisher Maryam , Thamer Ahlam , Shahata Shaheen , Atia Ahmed
Published: November 2024

Background

Since the emergence of the coronavirus pandemic in 2019, scientific studies have not stopped to understand the mechanism of several disorders that occurred in patients who were infected with the COVID-19 virus, among these disorders, the most important of which is high blood glucose because of its impact on human health. This study aimed to identify the association between blood glucose concentration and some biochemical variables that lead to high blood glucose in people infected with Covid-19 virus.

Methods

This study was conducted on 100 samples of serum of people who were confirmed to be infected with the COVID-19 virus using polymerase chain reaction (PCR) technology. Samples were collected from the Broccoli Isolation Center, the Respiratory Clinic, and the Sebha Medical Center in Sebha city, Libya. The concentration of glucose, insulin, cortisol, triglycerides, cholesterol, CRP and liver enzyme’s activity was measured.

Findings

The results showed that 60% of the patients had an increase in blood glucose concentration, and 40% of the patients had a normal glucose concentration. The levels of insulin, cortisol, CRP, triglycerides, and liver enzyme’s activity were compared between the two groups, and the results showed an increase in the mean concentration of cortisol, triglycerides, CRP and liver enzymes in the group of patients with high glucose concentration compared to the group of patients with a normal concentration of glucose, and the statistical analysis using the t-test showed that there were significant differences between the means (P = 0.000), while the mean insulin concentration was lower in the group of patients with elevated glucose level. The results also showed positive correlation between glucose and cortisol, triglycerides, CRP concentration and GPT, GOT activity.

Interpretation

Patients infected with the COVID-19 virus had elevated blood glucose concentration associated with decrease in their insulin hormone concentration. In addition, high concentration of biochemical variables that contribute to high blood glucose in patients infected with the COVID-19 virus were noticed.
Detection of human IgG antibodies againstMycoplasma genitaliumusing a recombinant MG075 antigen
Authors: Kildemoes Anna Overgaard , Rai Olivia Sureya Seierø , Westermann Elisabeth Probst Lyng , Johansen Henrik Frederik Bekkevold , Bjørnelius Eva , Anagrius Carin , Ma Liang , Rosenkrands Ida , Jensen Jørgen Skov
Published: November 2024

Mycoplasma genitaliumis a sexually transmitted pathogen, which can cause a range of reproductive tract diseases in both men and women. To disentangle the relationship betweenM. genitaliuminfection(s) and subsequent reproductive health complications at the population level, accurate serological tools are needed. The major challenge in developing specificM. genitaliumserological tests is the extensive cross-reactivity with the closely related ubiquitous respiratory tract pathogen,M. pneumoniae. In this report, we describe the development of an immunoblot assay based on a recombinant fragment of theM. genitaliumMG075 protein present in lipid-associated membrane extracts. A sensitivity of 87.1% was achieved based on testing antibody responses in sera from 101 adults with PCR-confirmedM. genitaliuminfection. A specificity of 95.2% was obtained through evaluation of sera from 166 children under 15 years of age with and withoutM. pneumoniaeinfection, who were unlikely to have been exposed to sexually transmittedM. genitalium. The development of a serological assay capable of accurately distinguishingM. genitaliumandM. pneumoniae, will enable a better understanding of associations betweenM. genitaliumand adverse reproductive sequelae.
Assessing the Limitations of Large Language Models in Clinical Practice Guideline-concordant Treatment Decision-making on Real-world Data
Authors: Roeschl Tobias , Hoffmann Marie , Hashemi Djawid , Rarreck Felix , Hinrichs Nils , Trippel Tobias D. , Gröschel Matthias I , Unbehaun Axel , Klein Christoph , Kempfert Jörg , Dreger Henryk , O’Brien Benjamin , Hindricks Gerhard , Balzer Felix , Falk Volkmar , Meyer Alexander
Published: November 2024

Aims

Large Language Models (LLMs) have shown promise in therapeutic decision-making comparable to medical experts, but these studies have used highly curated patient data. The aim of this study was to determine whether LLMs can make guideline-concordant treatment decisions based on patient data as it typically presents in clinical practice.

Methods and Results

We conducted a retrospective study of 80 patients with severe aortic stenosis who were scheduled for either surgical (SAVR, n=24) or transcatheter aortic valve replacement (TAVR, n=56) by our institutional heart team in 2022. Various LLMs (BioGPT, GPT-3.5, GPT-4, GPT-4 Turbo, GPT-4o, Llama-2, Mistral, PaLM 2, and DeepSeek-R1) were queried using either anonymized original medical reports or manually generated case summaries to determine the most guideline-concordant treatment. Agreement with the Heart Team was measured using Cohen’s kappa coefficients, reliability using intraclass correlation coefficients (ICCs), and fairness using frequency bias indices (FBIs) with FBIs >1 indicating bias towards TAVR. When presented with original medical reports, LLMs showed poor performance (kappa: −0.47–0.22, ICC: 0.0–1.0, FBI: 0.95–1.51). The LLMs’ performance improved substantially when case summaries were used as input and additional guideline knowledge was added to the prompt (kappa: −0.02–0.63, ICC: 0.01–1.0, FBI: 0.46–1.23). Qualitative analysis revealed instances of hallucinations in all LLMs tested.

Conclusion

Even advanced LLMs require extensively curated input for informed treatment decisions. Unreliable responses, bias and hallucinations pose significant health risks and highlight the need for caution in applying LLMs to real-world clinical decision-making.
Post-stroke changes in the ipsilesional motor area after contralesional continuous theta-burst stimulation
Authors: Vink Jord JT , Biemans Camille FM , van Lieshout Eline CC , van Eijk Ruben PA , Neggers Sebastiaan FW , Visser-Meily Johanna MA , van der Worp H Bart , Dijkhuizen Rick M
Published: November 2024

Background

Inhibitory repetitive transcranial magnetic stimulation (rTMS) of the contralesional primary motor cortex (M1) can promote upper limb recovery after stroke. However, its working mechanism remains unclear. We hypothesised that contralesional inhibitory rTMS increases ipsilesional M1 excitability and promotes ipsilesional motor-eloquent area (MEA) remapping.

Methods

Sixty patients who participated in a trial on contralesional continuous theta-burst stimulation (cTBS), an inhibitory form of rTMS, for the promotion of upper limb recovery after stroke, were included. M1 excitability and upper limb function were measured from TMS-based resting motor thresholds (RMTs) and the Fugl-Meyer Assessment (FMA) arm score, respectively, before cTBS treatment and at six follow-up visits up to one year after stroke. Forty-four patients additionally underwent longitudinal navigated TMS-based motor mapping. Remapping of the MEA was assessed from longitudinal changes in MEA overlap. Outcomes were analysed using mixed models for repeated measures.

Results

The ipsilesional RMT was 11% lower after active cTBS compared to sham cTBS (95% CI −18.7 to −2.6; p 0.0099) within twelve hours after the series of treatments. Compared to the sham cTBS group, MEA overlap was 27% (95% CI −44 to −11; p 0.0030), 25% (95% CI −45 to −5; p 0.0224) and 29% (95% CI −48 to −11; p 0.0038) less in the active cTBS group within twelve hours and at one week post-treatment, and three months post-stroke, respectively. Ipsilesional M1 excitability (i.e., RMT) within twelve hours post-cTBS correlated with FMA arm score at 3 months post-stroke (Spearman’s rho 0.59; p < 0.0001).

Conclusions

Upper limb recovery after cTBS treatment of the contralesional M1 after stroke may be caused by increased ipsilesional M1 excitability and MEA remapping.

Trial registration

https://trialsearch.who.int/; Unique identifier: NTR6133.
Validation of Segmental Bioelectrical Impedance Analysis Compared with Dual Energy X-Ray Absorptiometry to Measure Body Composition in Patients with Obesity-related Heart Failure with Preserved Ejection Fraction
Authors: Salmons Hannah , Ahmed Syed Imran , Billingsley Hayley , Reavey-Cantwell Alexander , Markley Roshanak , Golino Michele , Del Buono Marco Giuseppe , Damonte Juan Ignacio , Pinel Sebastian , Franco R. Lee , Abbate Antonio , Earthman Carrie P. , Carbone Salvatore
Published: November 2024

Background

Appendicular lean mass index (ALMI), a term used to describe appendicular lean soft tissue measured by dual-energy X-ray absorptiometry (DXA), is a major determinant of cardiorespiratory fitness in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Moreover, ALMI can be used to diagnose sarcopenia and sarcopenic obesity in this population. DXA is a reference standard for assessing body composition, however, segmental single-frequency bioelectrical impedance analysis (SF-BIA) could offer a more accessible, portable, cost-effective, and radiation-free alternative. To validate segmental SF-BIA for body composition analysis in patients with HFpEF and obesity, with a focus on ALMI.

Methods

We analyzed 62 consecutive euvolemic patients with persistent obesity-related HFpEF (83.8% female, 60.8± 2.8 years of age). We used both DXA and segmental SF-BIA to measure ALMI and appendicular fat mass index (AFMI), fat mass (FM), fat-free mass (FFM) in kg and as % of body weight, FM index, and FFM index. Correlations were assessed using Pearson’s coefficients and Bland-Altman plots, while linear regression was performed to evaluate proportional bias.

Results

Strong, statistically significant correlations were found between BIA and DXA for ALMI (r=0.897), AFMI (r=0.864), FM (r=0.968), FM% (r=0.867), FFM (r=0.954), and FFM% (r=0.852), FM index (r=0.97), and FFM index (r=0.88) (all p<0.001). The Bland-Altman analysis demonstrated agreement between methods and linear regression indicated no significant proportional bias for all parameters, except for AFMI.

Conclusions

Segmental SF-BIA-measured body composition shows strong correlations, appropriate agreements, and no proportional bias compared to DXA. Considering the central role of body composition and particularly of ALMI in patients with obesity-related HFpEF, when DXA is not readily available or contraindicated, segmental SF-BIA should be considered in this population.
Interventions for improving antibiotic prescribing in the community: systematic review and meta-analysis
Authors: Andrews Rebecca A J , Santiago Virginia Hernandez , Guthrie Bruce , Marwick Charis A
Published: November 2024

Background

Antibiotic resistance is a public health priority and antibiotic use in humans is a major contributing factor to its development. Interventions to improve antibiotic prescribing in the community, where most antibiotics are prescribed, are widely implemented with varying effect. The aim was to systematically review and meta-analyse evidence on effectiveness of different types of antibiotic prescribing interventions in the community.

Methods and Findings

Medline, Embase, and the Cochrane Central Register of Controlled Trials, were searched from database inception to 16 August 2021 to identify randomised controlled trials comparing antibiotic stewardship interventions versus usual care in community settings. Two reviewers screened studies, extracted data, and assessed risk of bias. Studies were grouped according to type of intervention. Meta-analyses employed random effects models. The outcome for meta-analyses was change in total antibiotic prescribing rates attributable to the intervention, compared to usual care, calculated as percentage differences. Other measures of change in antibiotic prescribing were included in narrative description.

Of 26,130 studies screened, 74 were included, with 53 comparisons from 45 studies meta- analysed. 50% of included studies had high risk of bias. Single interventions with statistically significant reductions in total antibiotic prescribing were point of care tests for antigen detection (−28.0% reduction, 95%CI−38.2 to−17.8); educational materials (−17.0%, −31.0 to - 3.0); printed decision-support systems (−10.8%,−15.7 to -6.0), educational workshops (− 8.7%,−12.8 to -4.7), and; educational outreach (−6.0%,−10.6 to−1.4). Multifaceted interventions were not more effective than single interventions (education + audit and feedback –9.9%, −12.8 to -7.0; other multifaceted -9.4%, −17.2 to −1.6). Effect sizes in sensitivity analyses excluding trials at high risk of bias were similar or larger.

Conclusions

Community antibiotic stewardship interventions were effective but with considerable variation in effect size. The most effective trial interventions may be more difficult to implement in practice, a key challenge for antibiotic stewardship.

Systematic review registrationPROSPERO CRD42014010160
PERCEPTIVE: an R Shiny pipeline for the prediction of epigenetic modulators in novel species
Authors: Small Eric M. , Steadman Christina R.
Published: November 2024

Epigenetic processes play key roles in regulating gene expression, genome stability, and metabolic output in organisms across the tree of life. Yet, the role epigenetics plays in regulating genomes and behaviors remains underdeveloped for microalgae, particularly as new species are identified and characterized. This is likely due to the cumbersome nature and species-dependent attributes of epigenetic wet-lab methodologies, which preclude the rapid identification of epigenetic modifications and modulators. However, there is extraordinary conservation of epigenetic processes from budding yeast to humans; in many cases, one may infer how behavior and function are epigenetically regulated in novel species by simply identifying epigenetic modulators, or the proteins responsible for conferring epigenetic modifications. To this end, we have developed a graphical software package, titled PERCEPTIVE (pipelinefor the prediction ofepigenetic modulators in novel species). This novel platform solely uses the genomic sequence of an organism, and preexisting information from model species, to predict the epigenetic modulators and associated modifications in a novel species. Predictions are presented to the user in a graphical interface, which provides literature-based interpretation of results, enabling users to quickly understand potential epigenetic processes in their species of interest and plan follow-up experiments. To test PERCEPTIVE, we predicted epigenetic modulators in several feedstock candidate algae species. To validate these predictions, wet-lab studies were performed, including mass spectrometry; these results underscore the high accuracy of PERCEPTIVE predictions. Overall, PERCEPTIVE represents a powerful tool for the research and manipulation of algal species, which does not requirea prioriknowledge of epigenetics and is accessible to a broad set of investigators.
Diminished gap junction coupling under diabetogenic conditions does not drive loss of functional β-cell sub-populations
Authors: Levitt Claire H , Isaacs Dominic , Hansen Maria S , Kravets Vira , Briggs Jennifer K , Benninger Richard KP
Published: November 2024

Within the islets of Langerhans, gap junction coupling is important for synchronizing oscillatory free-calcium activity ([Ca2+]) and regulating pulsatile insulin release. In islets from multiple models of diabetes, gap junction coupling is disrupted, and [Ca2+] synchronization and pulsatile insulin is lost. Functional sub-populations have been identified within the islet that are linked to driving synchronized [Ca2+] and insulin release. These sub-populations can be disrupted under conditions associated with diabetes such as glucolipotoxicity and inflammatory environments, and their loss may drive islet dysfunction. Here we investigate how loss of gap junction coupling influences functional subpopulations under diabetogenic environments. We treated islets with a cocktail of pro-inflammatory cytokines and specifically recovered gap junction coupling via co-treatment with a Cx36 mimetic peptide S293 that was previously shown to protect gap junction permeability and synchronized [Ca2+] dynamics. We performed calcium imaging and ChR2 stimulation, analyzed islet [Ca2+] dynamics and the presence of functional sub- populations including hubs and first-responders. 1h or 24h cytokine-treatment disrupted gap junction coupling, which was fully recovered by S293 peptide co-treatment. Treatment with pro- inflammatory cytokines decreased the recruitment of [Ca2+] upon ChR2 stimulation, increased the time between first and last responding cells upon glucose stimulation, and reduced the number and consistency of hub cells. When preserving gap junction coupling by S293 during cytokine treatment, the presence and consistency of these sub-populations was only marginally improved. We therefore concluded that restoration of gap junctions alone is not sufficient to recover functional sub-populations and their influence over islet function upon diabetogenic conditions associated with diabetes. Thus, preventing a disruption to intrinsic β-cell properties that define functional subpopulations is likely important for preserving these sub-populations during diabetes.
Testing hypotheses of skull function with comparative finite element analysis: three methods reveal contrasting results
Authors: Mitchell D. Rex , Wroe Stephen , Martin Meg , Weisbecker Vera
Published: November 2024

Comparative finite element analysis often involves standardising aspects of the models to test equivalent loading scenarios across species. However, in the context of feeding biomechanics of the vertebrate skull, what is considered “equivalent” can depend on the hypothesis. We use 13 skulls from diverse group of marsupial bettongs and potoroos (Potoroidae) to demonstrate that that scaling muscle forces to standardise unique aspects of biting mechanics can produce contrasting results of comparative stress or strain that are differentially suited to test specific kinds of hypotheses. We propose three categories of hypotheses for skull biting mechanics which each involve a unique method of muscle scaling: those comparing (1) the skull’s efficiency in distributing input muscle forces, via standardising input muscle force to size, (2) morphological biting adaptation through standardising mechanical advantage to simulate size-independent, equivalent bites, and (3) feeding ecology affected by size, such as niche partitioning, via standardising bite reaction force.

SUMMARY STATEMENT

Common approaches for scaling muscle forces in skull finite element models might not always offer reliable results for all hypotheses. We provide a framework for selecting the appropriate method.
Automatic Phenotyping Using Exhaustive Projection Pursuit
Authors: Moore Wayne A. , Meehan Stephen W. , Meehan Connor , Parks David R. , Walther Guenther , Herzenberg Leonore A.
Published: November 2024

One of the most common objectives in the analysis of flow cytometry data is the identification and delineation of phenotypes, distinct populations of cells with shared characteristics in the measurement dimensions. We have developed an automated tool to comprehensively identify these cell populations by Exhaustive Projection Pursuit (EPP). The method evaluates all two-dimensional projections among the suitable data dimensions and creates an optimized sequence of statistically significant gating regions that identify all phenotypes supported by the data. We evaluate the results of EPP on four well characterized datasets from the literature. The C++ for EPP can be called from any computing environment. We illustrate this with a MATLAB utility that integrates EPP with FlowJo. All source code is freely available.
Recovery and long-term health outcomes of SARS-CoV-2 infection in a prospective cohort in an urban setting, Kenya
Authors: Kisiangani Isaac , Ben Ângela Jornada , Wynberg Elke , Wami Welcome , Iddi Samuel , Kinya Idah , Vassall Anna , Kyobutungi Catherine , Ziraba Abdhalah , Njeru John , Mugenda Olive , Kiguoya-Njau Marion Wangui , Kimondo Mutambuki , Githua Geoffrey , de Jong Menno D. , Mohamed Shukri F. , Asiki Gershim , Schultsz Constance
Published: November 2024

Background

Evidence on Long COVID remains limited in sub-Saharan countries. This study aimed to explore the occurrence of COVID-19-related symptoms and factors affecting recovery and Long COVID severity in Nairobi, Kenya.

Methods

A prospective cohort of individuals testing positive for SARS-CoV-2 between February 2022 and February 2023 were followed until June 2023. COVID-19-related symptoms were assessed every three months. Time to recovery was analyzed using survival analysis, while factors affecting recovery and Long COVID severity using Cox proportional hazard and Poisson regression, respectively.

Results

42/291 (14%) participants had severe/critical SARS-CoV-2 infection, 59.1% were female and median age was 34. At 6 and 12 months post-positive PCR, 53.1% and 33.5% of participants had ≥1 COVID-19-related symptoms, respectively. Fatigue (40.2%), pain (36.8%), sore throat (36.8%), headaches (36.4%), and loss of strength (31.6%) were the most frequently reported COVID-19-related symptoms. Median time to recovery was longer in symptomatic participants with severe/critical SARS-CoV-2 infection than those with mild/moderate (234 vs 206 days respectively, p=0.016). Participants aged 40-64 years experienced slower recovery than those aged <40 years (aHR=0.635 [95%CI, 0.429;0.941]) and those with tertiary education recovered faster than those with primary education (aHR=1.869 [95%CI, 1.050;3.327]). Long COVID severity was associated with female sex (aIRR=1.413 [95%CI; 1.089;1.833]), tertiary education (aIRR, 0.525 [95%CI, 0.350;0.786]), and ≥1 comorbidity (aIRR=2.540 [95%CI, 1.377;4.687]).

Conclusions

Our findings suggest Long COVID presents a substantial, under-researched disease burden in Kenya. Risk factors for Long COVID are similar to those in high-income countries (HICs). Tailored prevention and support strategies for high-risk groups are needed.
Distinct subgroups in gastroparesis defined by simultaneous body surface gastric mapping and gastric emptying breath testing
Authors: Varghese Chris , Huang I-Hsuan , Schamberg Gabriel , Calder Stefan , Andrews Christopher N. , O’Grady Greg , Tack Jan , Gharibans Armen A
Published: November 2024

Background

Gastroparesis is a heterogeneous disorder with several contributing pathophysiologies. In this study we used simultaneous body surface gastric mapping (BSGM) and gastric emptying breath testing (GEBT) to subgroup patients with gastroparesis based on dynamic spectral meal response profiles and emptying rate.

Methods

Patients with chronic gastroduodenal symptoms and negative gastroscopy underwent simultaneous BSGM and gastric emptying breath test (GEBT) with 30 minutes fasting and 4 hours postprandial recording. In addition to standard metrics, the BSGM ‘Meal Response Ratio’ (MRR) compared amplitude in the first 2 hours postprandially to the subsequent 2 hours (lagged meal response ≤1).

Results

143 patients underwent simultaneous BSGM and GEBT (79% female, median age 31 years, median BMI 23 kg/m2). Delayed emptying occurred in 25.2% (n = 36). Those with a lagged meal response had longer T1/2(median 95.0 [IQR 59-373] vs median 78.0 [IQR 31-288], p=0.009) and higher rates of delayed emptying (42.9% vs 16.7% p = 0.03). BSGM phenotypes identified in patients with delayed emptying were: lagged meal response (25%), low gastric amplitude / rhythm stability (30.6%), elevated gastric frequencies (11.1%), and normal BSGM spectral analysis (33.3%). T1/2weakly correlated with worse total symptom burden score (r = 0.18, p = 0.03).

Conclusion

Combined BSGM and gastric emptying testing defines subgroups of gastroparesis based on contributing disease mechanisms, including a novel group with delayed post-prandial onset of gastric motor activity. Improved patient phenotyping in gastroparesis may enable improved therapeutic targeting through these biomarkers of disease processes.
Comprehensive analysis acrossSMN2excludes DNA methylation as an epigenetic biomarker for spinal muscular atrophy
Authors: Zwartkruis M.M. , Kortooms J.V. , Gommers D. , Elferink M.G. , Signoria I. , van der Sel J. , Hop P.J. , Zwamborn R.A.J. , Geene R. , Green J.W. , van Deutekom H.W.M. , van Rheenen W. , Veldink J.H. , Asselman F. , Wadman R.I. , van der Pol W.L. , van Haaften G.W. , Groen E.J.N.
Published: November 2024

Spinal muscular atrophy (SMA) is a severe neurodegenerative disease caused by defects in the survival motor neuron 1 (SMN1) gene. The wide variability in SMA severity is partially explained by an inverse correlation with copy number variation of the second humanSMNgene (SMN2). Nevertheless, significant variability in severity and treatment response remains unexplained, prompting a search for accessible biomarkers that could explain and predict this variability. DNA methylation ofSMN2has been proposed as one such biomarker, but comprehensive evidence and analyses are lacking. Here, we combined long-read nanopore sequencing with targeted bisulfite sequencing to enable high-resolution analysis ofSMN2-specific methylation patterns. We observed tissue-specific variation in DNA methylation across the entire 30 kbSMN2gene in 29 patients analyzed by long-read nanopore sequencing, identifying variable methylation patterns in the promoter, introns, and 3’ UTR. Subsequent targeted analysis of these regions by bisulfite sequencing of blood-derived DNA in 365 SMA patients showed no association betweenSMN2methylation and disease severity or treatment response, excluding blood methylation patterns as predictive biomarkers. However, we discovered significant age-associated variation inSMN2methylation, particularly in intron 1 and the 3’ UTR, highlighting DNA methylation as a possible modifier of SMN expression during development and aging. Our approach provides a broadly applicable strategy for detailed but cost-effective and high-throughput characterization of DNA methylation in other genes and diseases, including complex genetic regions.
Fine-mapping SLE-MHC associations revealed independent contributions of HLA missense variants andC4copy number variations
Authors: Yu Chae-Yeon , Shin Dong Mun , Kim Sung Min , Lee Yui Taek , Jeon Sungwon , Chun Sehwan , Bang So-Young , Lee Hye-Soon , Yin Xianyong , Cui Yong , Zhang Xuejun , Bhak Jong , Yoo Soon Ji , Kim Young Jin , Kim Bong-Jo , Bae Sang-Cheol , Kim Kwangwoo
Published: November 2024

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with strong genetic associations within the major histocompatibility complex (MHC) region. Despite significant advances, precisely pinpointing the genetic variants that contribute to SLE risk within the MHC remains challenging. This study aimed to comprehensively profile SLE-driving variants using a newly developed East Asian MHC imputation reference panel, capable of simultaneously imputing diverse MHC variants, including multi-level variants of HLA genes and copy number variations (CNVs) ofC4elements, with high imputation accuracy. Applying this panel to two SLE genome-wide association study datasets, we uncovered the independent contributions from six amino acid positions altering the epitope-binding surfaces of HLA-DRB1 and HLA-C. Additionally, reducedC4Acopy numbers and increased HERV copy numbers, collectively lowering C4 protein levels, were associated with increased SLE risk, independent of HLA variants. Our refined MHC-SLE association model provided superior explanations for SLE risk over previous association models. In summary, this study enhanced the understanding of HLA andC4in SLE pathogenesis and holds promise for advancing MHC association studies for immune-mediated inflammatory disorders in East Asians using our MHC panel (https://coda.nih.go.kr/usab/kis/intro.do).
Evaluation of the costs of care for pediatric patients hospitalized for RSV: a retrospective cohort study in Belgium
Authors: Tilmanne Anne , Pirson Magali , Leclercq Pol , Van Den Bulcke Julie , Bruyneel Arnaud
Published: November 2024

Objectives

This study aimed to evaluate the costs of respiratory-syncytial virus (RSV)-related hospitalizations in children under 3 years old in Belgium for hospitals and health insurance, and to identify factors influencing costs.

Study design

This retrospective cohort study used data from 16 French-speaking hospitals in Belgium, covering January 1, 2018, to December 31, 2019. RSV diagnoses for children under three were identified using International Classification of Diseases-Tenth Revision (ICD-10) codes, resulting in 2,176 hospitalizations analyzed for cost assessment. Hospital and health insurance costs were derived from administrative and billing data, adjusted for inflation, and analyzed using descriptive and inferential statistics, including regression models to assess cost factors.

Results

RSV prevalence among pediatric hospitalizations peaked at 12.9% in 2018 and 10.0% in 2019, with children under 3 years showing a prevalence of 16.7% both years. Of the 2,176 RSV-related hospitalizations, 61.8% were in children under one year, and 28.6% had readmissions within a year. The median length of stay (LOS) was 3.67 days, with a median hospital cost of €2,924 and a median health insurance cost of €2,221 per stay. Factors associated with higher costs included longer LOS, severe diagnosis-related group category, pediatric intensive care unit admission, and non-invasive ventilation use, with costs generally lower for children aged 1-2 years.

Conclusions

This study highlights the significant financial burden of RSV hospitalization in Belgium, with costs exceeding €25 million annually. This emphasizes the need for preventive measures and better resource allocation to reduce the economic impact of RSV on healthcare systems.
A Digital Biomarker Dataset in Hematopoietic Cell Transplantation: A Longitudinal Study of Caregiver-Patient Dyads (dHCT)
Authors: Jalin Aditya , Swatthong Nawat , Rozwadowski Michelle , Kumar Rajnish , Barton Deb , Braun Tom , Carlozzi Noelle , Hanauer David A. , Hassett Afton , Choi Sung Won
Published: November 2024

Background

Hematopoietic stem cell transplantation (HCT) is a potentially life-saving therapy for individuals with blood diseases, but involves a challenging recovery process that requires dedicated caregivers. The complex interplay between emotional distress, care partner (or unpaid caregiver) burden, and treatment outcomes necessitates comprehensive physiological and psychological measurements to fully understand these dynamics.

Findings

We collected longitudinal data from 166 HCT caregiver-patient dyads over 120 days post-transplant as part of a randomized controlled trial (NCT04094844). Data were gathered using the Fitbit® Charge 3 device, a custom mood-reporting app with positive psychology-based activities (Roadmap), PROMIS® health measures, and clinical events. The dataset includes minute-level heart rate, daily sleep metrics, step counts, self-reported mood scores, app usage metrics, PROMIS® T-scores (i.e. global health, depression), infection and readmission records, and clinical outcomes (e.g., acute and chronic graft-versus-host disease, relapse, mortality). Physiological data were available for both caregivers and patients. Data validation confirmed high compliance with mood reporting and the presence of physiological patterns between caregivers and patients that differed (i.e., lower activity in patients compared with caregivers across time).

Conclusions

This dataset offered an unprecedented view into the daily fluctuations of caregiver and patient well-being throughout the critical post-HCT period. It provided a valuable resource for researchers investigating the impact of mHealth app interventions, including emotional distress and physiological markers on treatment course and clinical outcomes. Our unique dataset informs interventions that may address caregiver support, patient care, or dyadic-focused strategies and enable novel analyses of single member or dyadic dynamics in HCT treatment.
Relation between motor competence and academic achievement: the mediating role of fitness and cognition in boys and girls
Authors: Fernández-Sánchez Antonio , Ruiz-Hermosa Abel , Redondo-Tébar Andrés , Díez-Fernández Ana , Martínez-Vizcaíno Vicente , Visier-Alfonso María Eugenia , Sánchez-López Mairena
Published: November 2024

Introduction

Good motor competence is linked to better academic achievement in schoolchildren, potentially mediated by fitness and cognition. However, the relative impact of these factors and whether they differ by sex remains unclear. The aim of the present study was to assess the mediating role of fitness components and executive function on this relationship, with a particular focus on sex differences.

Methods

This cross-sectional study included 562 schoolchildren (9-11 years, 293 girls) from Cuenca, Spain. We assessed gross motor competence (MABC-2 battery), fitness components (ALPHA battery), executive function (Toolbox battery), academic achievement (mean of language and mathematics grades), weight, height, and sociodemographic variables. Serial multiple mediation models between gross motor competence to AA through fitness and cognition were conducted using the Hayes’ PROCESS SPSS macro, both for the total sample and by sex.

Results

Both fitness and executive function partially mediated the relationship between gross motor competence and AA. In the total sample, the direct effect explained most of the total effect (51.22% to 72.68%), followed by the cognitive path (19.51% to 30.73%), fitness path (10.84% to 19.02%), and multiple path (4.43% to 9.27%). In boys, only the cognitive path mediated the relationship (56.35% to 68.91%), while in girls, the fitness path (for cardiorespiratory fitness and speed/agility, 19.08% and 20.27%), the cognitive path (limited to upper body strength, 14.92%), and the multiple path (for cardiorespiratory fitness, speed/agility, and lower body strength, 4.93%, 8.31% and 9.43%) were partial mediators.

Conclusions

Our results suggest that part of the effect found between gross motor competence and academic achievement in children occurs from improvements in fitness and executive function. These findings emphasize the need for motor competence programs that target both fitness (especially cardiorespiratory fitness and speed/agility) and executive function to boost academic achievement in children aged 9-11. Additionally, interventions should consider sex-specific differences.
Research on the Structural Characteristics and Evolution of China’s Medical and Health Innovation Cooperation Network Based on the Chinese Medical Science and Technology Awards
Authors: Xiaoqian Li , Fan Zhang , Junliang Zhang , Zhengfang Wang , Yue Yu , Huizheng Chen
Published: November 2024

Cooperative innovation is an important means to promote the development of medical and health undertakings. Based on the award data of the Chinese Medical Science and Technology Award from 2003 to 2022, this paper constructs an innovation cooperation network and uses social network analysis to explore the structure and evolution characteristics of China’s medical and health innovation cooperation network. The research shows that China’s medical and health innovation cooperation continues to increase, but the development of regional cooperation is not balanced; the scale of the network is expanding, and the small world effect is obvious, but the network density is relatively low, and there is still a large space for development of institutional innovation cooperation; Hospitals and universities play an important role in the network; The medical and health innovation cooperation network has the characteristics of community. Finally, policy suggestions are put forward from the aspects of strengthening regional balanced development, giving play to the radiation role of core institutions in the innovation cooperative network, and promoting diversified innovation cooperation, to form a balanced development innovation cooperation system, a robust innovation cooperation network ecology, and a stable innovation cooperation network structure.
Neurofilament light chain reference values in serum and cerebrospinal fluid: a bi-compartmental analysis in neurological diseases
Authors: Halbgebauer Steffen , Klose Veronika , Fazeli Badrieh , Klassen Paula , Alexudis Christoforos , Nagel Gabriele , Rosenbohm Angela , Rothenbacher Dietrich , de San Jose Nerea Gomez , Witzel Simon , Elmas Zeynep , Wiesenfarth Maximilian , Schuster Joachim , Dorst Johannes , Huss Andre , Bachhuber Franziska , Otto Markus , Landwehrmeyer G. Bernhard , Ludolph Albert C. , Tumani Hayrettin ,   the ALS Registry Swabia study group
Published: November 2024

Background

Concentrations of neurofilament light chain (NfL), a neuroaxonal damage marker, increase with age. Therefore, age-dependent reference values are important in clinical practice. However, so far these have only been established with a bead based system and age-dependent z-scores for CSF are missing. In addition, we here propose how the combined analysis of CSF and serum NfL could help in the discrimination between central (CNS) and peripheral nervous system (PNS) axonal degeneration.

Methods

For the calculation of age-reference values for serum and CSF 1514 NfL concentrations of control subjects determined with the microfluidic Ella system, were applied.

Results

Age-dependent NfL levels were calculated with additive quantile regression and presented with percentiles and z-scores. We observed a non-linear increase of NfL in serum and CSF. The spearman r of the association with age was 0.81 (95% CI: 0.78-0.83), p<0.0001 and 0.82 (95% CI: 0.79-0.85), p<0.0001 for serum and CSF NfL, respectively. Serum and CSF NfL levels were also associated with each other (r=0.68 (95%CI: 0.62-0.73), p<0.0001). Furthermore, we used this association to establish a bi-compartmental CSF and serum NfL model allowing to differentiate between peripheral or central origin of neurodegeneration.

Conclusions

The age-reference curves corroborate findings of an exponential elevation of NfL in serum and CSF with increasing age. As NfL values from different platforms are not interchangeable this is of additional high relevance. Moreover, the association between CSF and serum NfL values could be applied for clinical use regarding overlapping symptoms of CNS and PNS based neurological diseases.

What is already known on this topic

Neurofilament light chain levels in cerebrospinal fluid (CSF) and blood are widely accepted neuroaxonal damage markers which strongly correlate with age.

What this study adds

Age-dependent reference values and z-scores for both serum and CSF for the neurofilament light chain protein (NfL) using the microfluidic ELLA analysis platform. Novel approach for the discrimination between central and peripheral axonal damage using a bi-compartmental NfL model.

How this study might affect research, practice or policy

Easier and age-corrected interpretation of NfL values in clinical practice. Possibility to distinguish central from peripheral damage by analyzing both blood and CSF NfL.