bluuebunny/crossref_metadata_2025_split huggingface dataset:
When to expect scalp hair regrowth during treatment of severe alopecia areata with baricitinib: insights from trajectories analyses of patients enrolled in two phase III trials
Authors: King Brett , Shapiro Jerry , Ohyama Manabu , Egeberg Alexander , Piraccini Bianca Maria , Craiglow Brittany , Sinclair Rodney , Chen Yun-Fei , Wu Wen-Shuo , Ding Yuxin , Somani Najwa , Dutronc Yves 
Published: September 2023

Abstract

Background
Baricitinib is approved for the treatment of adults with severe alopecia areata (AA). In the absence of robust data on the patterns of regrowth during treatment of severe AA, there is a gap in the knowledge regarding treatment expectations.

Objectives
To examine whether different clinical response subgroups could be identified in baricitinib-treated patients with severe AA and factors that contribute to these subgroups.

Methods
The BRAVE-AA1 and BRAVE-AA2 phase III trials enrolled patients with severe AA [Severity of Alopecia Tool (SALT) score ≥ 50 (≥ 50% scalp hair loss)]. Patients randomized to baricitinib 4 mg or 2 mg retained their treatment allocation for 52 weeks. Based on patterns identified through growth mixture modelling (GMM), patients were categorized into responder subgroups according to when they first achieved ≥ 30% improvement from baseline in SALT score (SALT30). For each responder subgroup, trajectories of response (i.e. achievement of a SALT score ≤ 20, SALT score ≤ 10 and ≥ 50% change from baseline in SALT score) and baseline disease characteristics are reported.

Results
Respectively, 515 and 340 patients were randomized to once-daily baricitinib 4 mg and 2 mg at baseline; 69% and 51%, respectively, achieved SALT30 at least once by week 52. Based on GMM findings, we identified three responder subgroups: early (SALT30 by week 12), gradual (SALT30 after week 12–week 36) and late (SALT30 after week 36–week 52). The proportions of early, gradual and late responders and nonresponders were, respectively, 33%, 28%, 8% and 31% among patients treated with baricitinib 4 mg, and 20%, 23%, 9% and 49%, respectively, among those treated with baricitinib 2 mg. Early responders had a shorter trajectory to maximal clinical outcomes (e.g. &gt; 78% achieved a SALT score ≤ 20 by week 36) vs. gradual or late responders. Early responders were more frequent among patients with baseline severe AA (SALT score 50 to &lt; 95) vs. very severe AA (SALT score 95–100). Overall, responders (early to late) were more frequent in patients with short (&lt; 4 years) episodes of hair loss.

Conclusions
These analyses identified early, gradual and late responder subgroups for scalp hair regrowth in baricitinib-treated patients with severe AA, and that these subgroups are influenced by baseline characteristics. Findings from these analyses will help to inform treatment expectations for scalp hair regrowth.
IL-21, not IL-17A, exacerbates murine primary biliary cholangitis
Authors: Chan Chun-Wen , Chen Hung-Wen , Wang Yu-Wen , Lin Chia-I , Chuang Ya-Hui 
Published: September 2023

Abstract
Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease caused by intrahepatic bile duct injuries, resulting in fibrosis, cirrhosis, and eventually liver failure. T helper (Th) 17 cells are proposed to involve in the pathogenesis of PBC. However, how and which Th17 cell-derived cytokines affect PBC remains unclear. In this study, we investigated the effects of Th17 effector cytokines, including interleukin (IL)-17A, IL-17F, and IL-21 in PBC using a xenobiotic-induced mouse model of autoimmune cholangitis (inducible chemical xenobiotic models of PBC) treated with cytokine-expressing adeno-associated virus. Our results showed that administration of IL-17A, the well-known main cytokine produced by Th17 cells, did not augment liver inflammation or fibrosis. In contrast, we noted IL-17A-treated mice had lower hepatic Th1 cell numbers and higher hepatic CD11b+Ly6G+ polymorphonuclear myeloid-derived suppressor cell numbers. IL-17F did not alter liver inflammation or fibrosis. However, the administration of IL-21 exacerbated liver inflammatory responses and portal cell infiltration. IL-21 markedly increased the numbers of activated CD8+ T cells and liver tissue-resident memory CD8+ T cells. Moreover, IL-21 aggravates liver fibrosis in mice with autoimmune cholangitis. These results emphasized that not IL-17A but IL-21 in Th17 cell-derived cytokines affected the pathogenesis of PBC. IL-21 enhanced liver inflammation and progression to fibrosis by enhancing the numbers and effector activities of CD8+ T cells. Delineation of the effects of different Th17 effector cytokines in PBC offers clues for developing new therapeutic approaches.
Cardiomyocyte and endothelial cells play distinct roles in the tumour necrosis factor (TNF)-dependent atrial responses and increased atrial fibrillation vulnerability induced by endurance exercise training in mice
Authors: Lakin Robert , Polidovitch Nazari , Yang Sibao , Parikh Mihir , Liu Xueyan , Debi Ryan , Gao Xiaodong , Chen Wenliang , Guzman Camilo , Yakobov Simona , Izaddoustdar Farzad , Wauchop Marianne , Lei Qian , Xu Weimin , Nedospasov Sergei A , Christoffels Vincent M , Backx Peter H 
Published: September 2023

Abstract

Aims
Endurance exercise is associated with an increased risk of atrial fibrillation (AF). We previously established that adverse atrial remodelling and AF susceptibility induced by intense exercise in mice require the mechanosensitive and pro-inflammatory cytokine tumour necrosis factor (TNF). The cellular and mechanistic basis for these TNF-mediated effects is unknown.

Methods and results
We studied the impact of Tnf excision, in either atrial cardiomyocytes or endothelial cells (using Cre-recombinase expression controlled by Nppa or Tie2 promoters, respectively), on the cardiac responses to six weeks of intense swim exercise training. TNF ablation, in either cell type, had no impact on the changes in heart rate, autonomic tone, or left ventricular structure and function induced by exercise training. Tnf excision in atrial cardiomyocytes did, however, prevent atrial hypertrophy, fibrosis, and macrophage infiltration as well as conduction slowing and increased AF susceptibility arising from exercise training. In contrast, endothelial-specific excision only reduced the training-induced atrial hypertrophy. Consistent with these cell-specific effects of Tnf excision, inducing TNF loss from atrial cardiomyocytes prevented activation of p38MAPKinase, a strain-dependent downstream mediator of TNF signalling, without affecting the atrial stretch as assessed by atrial pressures induced by exercise. Despite TNF’s established role in innate immune responses and inflammation, neither acute nor chronic exercise training caused measurable NLRP3 inflammasome activation.

Conclusions
Our findings demonstrate that adverse atrial remodelling and AF vulnerability induced by intense exercise require TNF in atrial cardiomyocytes whereas the impact of endothelial-derived TNF is limited to hypertrophy modulation. The implications of the cell autonomous effects of TNF and crosstalk between cells in the atria are discussed.
Validation of the IBD-Control Questionnaire across different sociodemographic and clinical subgroups: secondary analysis of a nationwide electronic survey
Authors: Gebeyehu Gerum G , Taylor Frederick , Dobson Liz , Cummings J R Fraser , Bloom Stuart , Kennedy Nicholas A , Christiansen Paul , Bodger Keith 
Published: September 2023

Abstract

Background
The IBD-Control Questionnaire is a simple, generic measure of patient-perceived disease control used increasingly in clinical practice and research. We aimed to address knowledge gaps in its psychometric performance, to ensure that it can be used with confidence in a variety of contexts.

Methods
We analysed 7341 responses to the IBD Registry COVID-19 survey, sent to 40 911 patients who completed an online self-assessment tool during the pandemic. Questions covered demographics, comorbidities, inflammatory bowel disease [IBD] sub-type, and IBD-Control Questionnaire and symptom scores [CD-PRO2 or UC-PRO2]. Psychometric properties of IBD-Control-8 were tested overall and within subgroups (Crohn’s disease [CD], ulcerative colitis [UC] and IBD unclassified; male and female; ≤65 and &gt;65 years; number of co-morbidities; deprivation status).

Results
Internal consistency was very strong overall [α: 0.84, ω: 0.89] and for each subgroup [α range: 0.81–0.85; ω: 0.86–0.90]. Construct validity was demonstrated by moderate correlation of each item with global rating [VAS] [rs range: 0.47–0.65], strong correlation between IBD-Control-8 score and VAS [rs = 0.74], moderate-to-strong with PRO2 scores [CD: rs = −0.718; UC: rs = −0.602] and significantly higher IBD-Control-8 scores for PRO2-remission vs PRO2-active, consistent across subgroups. Exploratory and confirmatory factor analyses demonstrated a two-factor model (items loading onto ‘Health-related Quality of Life’ [HRQoL] or ‘Treatment’ domains). Extensive tests for factorial invariance confirmed consistency.

Conclusions
IBD-Control-8 is a psychometrically robust scale which can be used across a range of populations. It offers a quick, reliable, and valid method of assessing patient-perceived control. The construct of ‘control’ includes traditional HRQoL and a novel domain relating to treatment perception.
Temporary Faecal Diversion for Refractory Perianal and/or Distal Colonic Crohn’s Disease in the Biologic Era: An Updated Systematic Review with Meta-analysis
Authors: Jew Michael , Meserve Joseph , Eisenstein Samuel , Jairath Vipul , McCurdy Jeffrey , Singh Siddharth 
Published: September 2023

Abstract

Background and Aims
We evaluated short- and long-term outcomes of temporary faecal diversion [FD] for management of refractory Crohn’s disease [CD], focusing on outcomes in the biologic era.

Methods
Through a systematic literature review until March 15, 2023, we identified 33 studies [19 conducted in the biologic era] that evaluated 1578 patients with perianal and/or distal colonic CD who underwent temporary FD [with intent of restoring bowel continuity] and reported long-term outcomes [primary outcome: successful restoration of bowel continuity, defined as remaining ostomy-free after reconnection at a minimum of 6 months after diversion or at the end of follow-up]. We calculated pooled rates (with 95% confidence interval [CI]) using random effects meta-analysis, and examined factors associated with successful restoration of bowel continuity.

Results
Overall, 61% patients [95% CI, 52-68%; 50% in biologic era] experienced clinical improvement after FD. Stoma takedown was attempted in 34% patients [28–41%; 37% in biologic era], 6–18 months after diversion. Among patients where bowel restoration was attempted, 63% patients [54–71%] had successful restoration of bowel continuity, and 26% [20–34%] required re-diversion. Overall, 21% patients [17–27%; 24% in biologic era] who underwent FD were successfully restored; 34% patients [30–39%; 31% in biologic era] required proctectomy with permanent ostomy. On meta-regression, post-diversion biologic use and absence of proctitis was associated with successful bowel restoration after temporary FD in contemporary studies.

Conclusion
In the biologic era, temporary FD for refractory perianal and/or distal colonic CD improves symptoms in half the patients, and bowel continuity can be successfully restored in a quarter of patients.
Noninvasive assessment of left ventricular end-diastolic pressure using machine learning–derived phasic left atrial strain
Authors: Gruca Martin M , Slivnick Jeremy A , Singh Amita , Cotella Juan I , Subashchandran Varun , Prabhu David , Asch Federico M , Siddiki Mikail , Gupta Nikhil , Mor-Avi Victor , Su Jimmy L , Lang Roberto M 
Published: September 2023

Abstract

Aims
While transthoracic echocardiography (TTE) assessment of left ventricular end-diastolic pressure (LVEDP) is critically important, the current paradigm is subject to error and indeterminate classification. Recently, peak left atrial strain (LAS) was found to be associated with LVEDP. We aimed to test the hypothesis that integration of the entire LAS time curve into a single parameter could improve the accuracy of peak LAS in the noninvasive assessment of LVEDP with TTE.

Methods and results
We retrospectively identified 294 patients who underwent left heart catheterization and TTE within 24 h. LAS curves were trained using machine learning (100 patients) to detect LVEDP ≥ 15 mmHg, yielding the novel parameter LAS index (LASi). The accuracy of LASi was subsequently validated (194 patients), side by side with peak LAS and ASE/EACVI guidelines, against invasive filling pressures. Within the validation cohort, invasive LVEDP was elevated in 116 (59.8%) patients. The overall accuracy of LASi, peak LAS, and American Society of Echocardiography/European Association for Cardiovascular Imaging (ASE/EACVI) algorithm was 79, 75, and 76%, respectively (excluding 37 patients with indeterminate diastolic function by ASE/EACVI guidelines). When the number of LASi indeterminates (defined by near-zero LASi values) was matched to the ASE/EACVI guidelines (n = 37), the accuracy of LASi improved to 87%. Importantly, among the 37 patients with ASE/EACVI-indeterminate diastolic function, LASi had an accuracy of 81%, compared with 76% for peak LAS.

Conclusion
LASi allows the detection of elevated LVEDP using invasive measurements as a reference, at least as accurately as peak LAS and current diastolic function guideline algorithm, with the advantage of no indeterminate classifications in patients with measurable LAS.
Long-term comparison of the efficacy of manual versus powered tooth brushing in adolescent orthodontic patients: a single-centre, parallel design randomized clinical trial
Authors: Johal Ama , Shagmani Muftah , Alfuraih Omar , Arad Ian 
Published: September 2023

Abstract

Background and objectives
To-date, there is no evidence comparing the long-term efficacy of powered and manual toothbrushes in adolescents undergoing fixed appliance treatment. The trial compared the efficacy of manual versus powered toothbrush in controlling plaque and gingival health in patients undergoing fixed treatment in respect of both the short- and long-term.

Trial design
This was a randomized, parallel, controlled single-blind clinical trial, undertaken in a hospital setting, for which the consolidated standards of reporting trials guidelines were followed.

Methods
Ninety-two adolescent participants planned to undergo fixed appliance therapy, were randomly assigned to either a manual or powered toothbrush, with allocation concealment. The outcome measures were plaque and gingival indices and bleeding on probing, assessed at baseline (prior to fixed appliance), one-, six- and 12-months.

Results
The final sample included 84 participants, aged 12-18 (M=14.1, SD=1.93) years, with 40 (47%) were using a manual and 44 (52%) a powered toothbrush. The intervention (powered vs. manual toothbrush) itself appeared insignificant with regards to the gingival index (GI) (95%CI −0.1 – 0.03; P=0.26), plaque index (PI) (95%CI −0.13 – 0.14; P=0.93) and bleeding on probing (BoP) (95%CI −0.03 – 0.03; P=0.98) at any of the time points assessed. However, periodontal health indicators and plaque control significantly worsened (p&lt;0.01), over the 12-month follow-up period, following placement of the fixed appliances placement.

Conclusion
Whilst no differences were found between manual and powered toothbrushes in controlling plaque and gingival health, in participants undergoing fixed orthodontic treatment, both were suboptimal and highlighted the need for greater patient support and monitoring.

Trial registration details
https://doi.org/10.1186/ISRCTN74268923 Trial funding: Colgate-Palmolive (USA)
Optimizing patient selection for primary prevention implantable cardioverter-defibrillator implantation: utilizing multimodal machine learning to assess risk of implantable cardioverter-defibrillator non-benefit
Authors: Kolk Maarten Z H , Ruipérez-Campillo Samuel , Deb Brototo , Bekkers Erik J , Allaart Cornelis P , Rogers Albert J , Van Der Lingen Anne-Lotte C J , Alvarez Florez Laura , Isgum Ivana , De Vos Bob D , Clopton Paul , Wilde Arthur A M , Knops Reinoud E , Narayan Sanjiv M , Tjong Fleur V Y 
Published: September 2023

Abstract

Aims
Left ventricular ejection fraction (LVEF) is suboptimal as a sole marker for predicting sudden cardiac death (SCD). Machine learning (ML) provides new opportunities for personalized predictions using complex, multimodal data. This study aimed to determine if risk stratification for implantable cardioverter-defibrillator (ICD) implantation can be improved by ML models that combine clinical variables with 12-lead electrocardiograms (ECG) time-series features.

Methods and results
A multicentre study of 1010 patients (64.9 ± 10.8 years, 26.8% female) with ischaemic, dilated, or non-ischaemic cardiomyopathy, and LVEF ≤ 35% implanted with an ICD between 2007 and 2021 for primary prevention of SCD in two academic hospitals was performed. For each patient, a raw 12-lead, 10-s ECG was obtained within 90 days before ICD implantation, and clinical details were collected. Supervised ML models were trained and validated on a development cohort (n = 550) from Hospital A to predict ICD non-arrhythmic mortality at three-year follow-up (i.e. mortality without prior appropriate ICD-therapy). Model performance was evaluated on an external patient cohort from Hospital B (n = 460). At three-year follow-up, 16.0% of patients had died, with 72.8% meeting criteria for non-arrhythmic mortality. Extreme gradient boosting models identified patients with non-arrhythmic mortality with an area under the receiver operating characteristic curve (AUROC) of 0.90 [95% confidence intervals (CI) 0.80–1.00] during internal validation. In the external cohort, the AUROC was 0.79 (95% CI 0.75–0.84).

Conclusions
ML models combining ECG time-series features and clinical variables were able to predict non-arrhythmic mortality within three years after device implantation in a primary prevention population, with robust performance in an independent cohort.
Interkingdom network analyses reveal microalgae and protostomes as keystone taxa involved in nutrient cycling in large freshwater lake sediment
Authors: Li Zhidan , Sun Liang , Liu Sijie , Lei Peng , Wang Rui , Li Sha , Gu Yian 
Published: September 2023

Abstract
Few studies have explored the role of interkingdom interactions between bacteria and microeukaryotes in nutrient cycling in lake ecosystems. We conducted sediment sampling from 40 locations covering Hongze Lake and analyzed their chemical properties. Intra- and interkingdom networks were constructed using 16S and 18S rRNA gene amplicon sequencing. Microeukaryotic intranetworks were more complex in spring than in autumn, while no clear variation in the complexity of bacterial intranetworks was found between autumn and spring. Larger and more complex bacterial–microeukaryotic bipartite networks emerged in spring than in autumn, correlated with lower carbon, nitrogen, and phosphorus levels in spring, likely resulting in intense microbial competition. Bacteria and microeukaryotes played different topological roles in interkingdom networks, with microeukaryotes contributing to the networks’ greater complexity. Seven keystone modules were identified in spring and autumn nutrient cycling. Importantly, keystone taxa in these modules belonged to photoautotrophic microalgae or predatory protostomes, indicating that these organisms are key drivers in lake sediment nutrient cycling. Our results suggested that nutrient content variation in autumn and spring changes interkingdom networks’ topological structure between bacteria and microeukaryotes. Microalgae and protostomes are essential in freshwater lake nutrient cycling and may be targeted to modulate nutrient cycling in large freshwater ecosystems.
Isolation of heavy metal-resistantStaphylococcus epidermidisstrainTWSL_22and evaluation of heavy metal bioremediation potential of recombinantE. colicloned with isolatedcadD
Authors: Dissanayake D M D C , Kumari W M N H , Chandrasekharan N V , Wijayarathna C D 
Published: September 2023

AbstractA heavy metal-resistant bacterial strain, TWSL_22 was isolated from an industrial effluent sample and tested for heavy metal tolerance and resistance. The strain was molecularly characterized as Staphylococcus epidermidis based on 16S rDNA gene analysis and the sequence was deposited in the NCBI repository (accession number KT184893.1). Metal removal activity (P &lt; .001) of TWSL_22 was 99.99 ± 0.001%, 74.43 ± 2.51%, and 51.16 ± 4.17% for Cd, Pb, and Cu, respectively. Highest MIC was observed for Cd. Antibiotic susceptibility assays revealed the strain TWSL_22 to be resistant to several antibiotics. The strain was screened for possible heavy metal-resistant genes and presence of cadA, copA, and cadD was confirmed by PCR. A DNA fragment containing complete sequence of cadD (618 bp) was isolated and cloned into pET 21a(+), transformed into E. coli BL21 and designated as E. coli/cadDET. E. coli/cadDET showed high metal tolerance capacity and could remove over 82% of heavy metals (Zn2+, Cd2+, Cu2+, and Cr3+) in the industrial effluent.
Genomic Mysteries of Giant Bacteria: Insights and Implications
Authors: Ionescu Danny , Volland Jean-Marie , Contarini Paul-Emile , Gros Olivier 
Published: September 2023

AbstractBacteria and Archaea are traditionally regarded as organisms with a simple morphology constrained to a size of 2–3 µm. Nevertheless, the history of microbial research is rich in the description of giant bacteria exceeding tens and even hundreds of micrometers in length or diameter already from its early days, for example, Beggiatoa spp., to the present, for example, Candidatus Thiomargarita magnifica. While some of these giants are still being studied, some were lost to science, with merely drawings and photomicrographs as evidence for their existence. The physiology and biogeochemical role of giant bacteria have been studied, with a large focus on those involved in the sulfur cycle. With the onset of the genomic era, no special emphasis has been given to this group, in an attempt to gain a novel, evolutionary, and molecular understanding of the phenomenon of bacterial gigantism. The few existing genomic studies reveal a mysterious world of hyperpolyploid bacteria with hundreds to hundreds of thousands of chromosomes that are, in some cases, identical and in others, extremely different. These studies on giant bacteria reveal novel organelles, cellular compartmentalization, and novel mechanisms to combat the accumulation of deleterious mutations in polyploid bacteria. In this perspective paper, we provide a brief overview of what is known about the genomics of giant bacteria and build on that to highlight a few burning questions that await to be addressed.