bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using patient preference to inform ritlecitinib dose selection for alopecia areata treatment
Authors: Hauber Brett , Whichello Chiara , Mauer Jonathan , Law Ernest , Trapali Myrto , Whalen Edward , Wajsbrot Dalia , Krucien Nicolas , Tervonen Tommi , Zwillich Samuel H. , Wolk Robert 
Published: January 2025

AbstractRitlecitinib is an oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma (JAK3/TEC) family kinase inhibitor approved for the treatment of severe alopecia areata (AA). Benefit–risk profiles of two doses of ritlecitinib (50 mg vs 30 mg once daily) were evaluated by integrating patient preferences and clinical efficacy and safety estimates for ritlecitinib. A discrete‐choice experiment (DCE) was utilized to elicit preferences for benefit and safety attributes of systemic AA treatments. Benefits included probabilities of ≥80% scalp hair coverage and achieving moderate to normal eyebrows and eyelashes. Potential risks included 3‐year probabilities of serious infection, cancer, and blood clots. Preference estimates were used to calculate the maximum acceptable risk (MAR) that patients would accept for expected increases in benefit from choosing a higher ritlecitinib dose over a lower dose. Ritlecitinib benefits were calculated from the ALLEGRO‐2b/3 clinical trial. MARs were calculated separately for each risk and jointly for all possible combinations. Adults (n = 201) with physician‐confirmed ≥50% scalp hair loss from AA participated. To achieve expected increases in the probabilities of ≥80% scalp hair coverage or moderate to normal eyebrows and eyelashes when choosing 50 mg over 30 mg of ritlecitinib, patients would be willing to accept increases in each 3‐year risk up to a mean of 3.88 absolute percentage points (95% confidence interval [CI], 2.86–4.90) for serious infection, 1.63 (95% CI, 1.08–2.18) for cancer, and 5.30 (95% CI, 3.60–7.00) for blood clots. These results, combined with the estimated differences in risks between the two doses, indicate that patients with AA value increases in the probabilities of scalp, eyebrow, and eyelash hair regrowth, with the average patient accepting increases in potential treatment‐related risks for the 50‐mg dose in exchange for higher efficacy than 30 mg. The DCE approach to measuring risk tolerance, combined with comparisons to expected benefit and risk differences, can be used to optimize AA treatment dose selection.
Schlafen 11 Expression in Patients With Small Cell Lung Cancer and Its Association With Clinical Outcomes
Authors: Masuda Ken , Yoshida Tatsuya , Motoi Noriko , Shinno Yuki , Matsumoto Yuji , Okuma Yusuke , Goto Yasushi , Horinouchi Hidehito , Yamamoto Noboru , Watanabe Shun‐ichi , Hoshino Tomoaki , Yatabe Yasushi , Ohe Yuichiro 
Published: January 2025

ABSTRACTBackgroundSchlafen 11 (SLFN‐11) has been identified as a sensitizer of tumor cells to DNA‐damaging agents. However, the relationship between SLFN‐11 expression and clinical outcomes in patients with small cell lung cancer (SCLC) remains unexplored. Thus, we aimed to evaluate the impact of SLFN‐11 expression on survival in patients with limited‐stage (LS) SCLC.MethodsWe conducted a retrospective review of data from patients pathologically diagnosed with LS‐SCLC post‐surgery between January 2008 and December 2018. SLFN‐11 expression was assessed using immunohistochemistry in tissue microarrays and scored using a histology (H)‐score (range: 0–300).ResultsOverall, 86 patients were included in the analysis with a median H‐score of 43 for SLFN‐11 expression. Among the patients, 44 had high SLFN‐11 expression (provisionally defined as H‐score ≥ 43). No significant differences in clinical profiles were observed between the two groups (high and low SLFN expression). The median survival durations were not reached (NR; 95% confidence interval [CI]: 65.1 months to NR) and 33.5 months (95% CI: 24.2 months to NR) for patients with high and low SLFN‐11 expression, respectively (hazard ratio [HR]: 0.40, 95% CI: 0.19–0.81; p = 0.012). Among patients who relapsed post‐surgery (n = 21), the median survival durations were 22.0 (95% CI: 7.6–44.9 months) and 8.1 (95% CI: 1.8–24.6 months) months in patients with high and low SLFN‐11 expression, respectively (HR: 0.22, 95% CI: 0.06–0.84; p = 0.026).ConclusionsHigh SLFN‐11 expression is associated with relatively longer survival in patients with LS‐SCLC in both those undergoing surgery and those who have relapsed.
Evaluating Lichen Sclerosus in Phimosis: Insights From a Multidisciplinary Retrospective Study
Authors: Bighetti Stefano , Mancon Stefano , Suardi Nazareno , Calzavara‐Pinton Piergiacomo , Maione Vincenzo , Arisi Mariachiara , Lughezzani Giovanni , Zerbinati Nicola , Ghini Iacopo , Bettolini Luca 
Published: January 2025

ABSTRACTObjectivesThis study aimed to evaluate the prevalence of lichen sclerosus (LS) in male patients undergoing circumcision for phimosis, emphasising the significance of a multidisciplinary approach in the early diagnosis and management of this condition.MethodsA retrospective analysis was performed on 841 male patients who underwent circumcision at a high‐volume medical centre between 2001 and 2023. Data were collected on clinical diagnoses made by both dermatologists and urologists, along with the corresponding histological findings. Logistic regression models were utilised to assess diagnostic accuracy and the relationship between clinical suspicion and histological confirmation.ResultsHistological confirmation of LS was identified in 30.6% of the cases. Dermatologists demonstrated a diagnostic accuracy of 81.8%, whereas urologists showed an accuracy of 46.1%. The evaluations conducted by dermatologists exhibited a significant correlation with histological confirmation of LS (odds ratio 4.81; 95% confidence interval: 1.96–11.80; p = 0.001).ConclusionsThis study elucidates the differences in diagnostic accuracy between dermatologists and urologists in identifying LS in patients undergoing circumcision for phimosis, highlighting the necessity of a multidisciplinary approach to improve the diagnostic process. Furthermore, the epidemiological data obtained from this research offer valuable insights into the prevalence of LS and the associated diagnostic challenges within a substantial patient cohort.
Nuance and specificity always matter—Especially for all the meanings of ‘gender’: A reply to Jackson and Bussey (2024)
Authors: Tate Charlotte Chucky 
Published: January 2025

AbstractJackson and Bussey (The British Journal of Psychology, 2024, 115, 723) present the provocative argument that the concept of a “true gender” is not a useful conceptual object for psychology. While the article does make 2 valid and worthwhile points, the remainder of that article lacks necessary nuance in developing its general conclusion.
Lateralizing value of interictal epileptiform discharges and other parameters in hypothalamic hamartoma
Authors: Niedermoser Friederike , Metzger Sarah M. , Wagner Kathrin , Reinacher Peter C. , Schönberger Jan , Jacobs‐LeVan Julia , Schulze‐Bonhage Andreas , Klotz Kerstin Alexandra 
Published: January 2025

AbstractObjectiveHypothalamic hamartomas (HHs) are associated with pharmacoresistant epilepsy. Stereotactic radiofrequency thermocoagulation (SRT) shows promise as a disconnecting intervention. Although magnetic resonance imaging (MRI) is typically used to determine the attachment and intervention side, it presents challenges in cases of bilaterally attached HH, where the epileptogenic side is unclear. The lateralizing potential of electroclinical parameters in such cases remains uncertain. This retrospective study evaluates the lateralization value of specific parameters, particularly in patients with unilateral HH, to improve future diagnostics and treatment approaches for bilateral HH.MethodsFour lateralizing parameters—semiology, ictal electroencephalography (EEG), and interictal epileptiform discharges during awake (IEDsw) and sleep states (IEDss)—were assessed for correlation with HH attachment side using Spearman's ρ. We calculated areas under the curves (AUCs) and cutoffs for left and right IEDs prognostic lateralizing value, plotting differences between IEDsright and IEDsleft in a receiver‐operating characteristic(ROC) curve to establish the required preponderance of unilateral IEDss to differentiate between left and right HHs. Binomial logistic regression was employed to predict the HH attachment side.ResultsWe included 25 patients (2–55 years of age) with mainly unilateral (n = 22) HHs who underwent SRT and presurgical evaluation. All parameters correlated with HH attachment side (semiology R = −.62, p = .005; ictal EEG R = .51, p = .047; IEDs R = .55, p = .018; IEDw, R = .61, p = .018). AUC values for right and left IEDs were .76 (p = .047) and .85 (p = .019), respectively, with cutoffs of .34 and .15. The AUC for “IEDsright–IEDsleft” was .98 (p = .0018) with a cutoff of .16. IEDss and semiology were significant predictors, achieving 88% correct lateralization.SignificanceIEDss are promising biomarkers for HH lateralization in unilateral HH. The predominance of unilateral IEDss suggests ipsilateral HH. Even in cases with predominantly bilateral IEDss, a slight preponderance of unilateral IEDss can indicate the attachment side. In addition, combining IEDss and semiology provides a predictive model for HH lateralization.
Factor VIII Antibodies Demonstrate Type I or Type II Kinetics in Acquired Haemophilia A
Authors: Kamel Kirollos , Sardo Infirri Sofia , Riddell Anne , Chowdary Pratima , Batty Paul 
Published: January 2025

ABSTRACTBackgroundAcquired haemophilia A (AHA) is an acquired bleeding disorder resulting from autoantibodies against Factor VIII (FVIII). Previous studies have reported differences in FVIII inhibitor kinetics (type I or type II) in AHA compared to severe haemophilia A.AimTo characterise inhibitor kinetics in AHA and evaluate the proportions displaying type I, II or indeterminate kinetics.MethodsSingle‐centre retrospective study of inhibitor kinetics in adults with AHA. Type I kinetics were defined as linear FVIII inhibition with ≥ 97% FVIII inactivation. Type II kinetics were defined as non‐linear kinetics and inability to completely neutralise FVIII. Inhibitor titres were calculated using two methods outlined by the International Council for Standardisation in Haematology.ResultsBaseline samples from 34 patients were included. Fifteen samples (44.1%) exhibited type I kinetics, 16 samples (47.1%) exhibited type II kinetics and 3 (8.8%) were indeterminate. Plateau mean residual FVIII:C was higher for inhibitors displaying type II compared to type I kinetics (18.6 vs. 2.9 IU/dL, p < 0.0001). Non‐linear regression using a dose‐response curve without categorisation for kinetics type yielded a poor fit (R2 = 38%), which improved with refitting using categories of type I or II kinetics that explained 87% and 85% of the variability. The median difference in inhibitor titre between the two reporting methods was 5% and 15% in the type I and II kinetics groups, respectively.ConclusionFVIII autoantibodies demonstrate either type I or type II kinetics. Greater discrepancy in reported inhibitor titres depending on the method used is seen for inhibitors with type II kinetics.
Evaluating two rechallenge strategies of immune checkpoint inhibitors: Durvalumab plus tremelimumab in advanced hepatocellular carcinoma
Authors: Yonemoto Takuya , Ogasawara Sadahisa , Kanogawa Naoya , Miwa Chihiro , Fujiya Makoto , Tsuchiya Takahiro , Sawada Midori , Akatsuka Teppei , Izai Ryo , Yumita Sae , Nakagawa Miyuki , Okubo Tomomi , Koroki Keisuke , Inoue Masanori , Nakamura Masato , Kondo Takayuki , Nakamoto Shingo , Itokawa Norio , Atsukawa Masanori , Itobayashi Ei , Moriguchi Michihisa , Kato Naoya 
Published: January 2025

AbstractAimThis study aimed to evaluate the safety and efficacy of durvalumab plus tremelimumab in patients with advanced hepatocellular carcinoma who have previously received atezolizumab plus bevacizumab (Atez/Bev). Additionally, it seeks to assess the feasibility of administering immunotherapy after the occurrence of immune‐mediated adverse events (imAEs) in real‐world clinical practice.MethodsThis retrospective study analyzed data from patients with advanced hepatocellular carcinoma treated with durvalumab plus tremelimumab at four Japanese institutions. Clinical outcomes, adverse events, tumor dynamics, and serum cytokine and chemokine levels were evaluated, with a focus on efficacy following prior Atez/Bev treatment.ResultsDurvalumab plus tremelimumab was administered to 68 patients. The objective response rate was 10.3%, and the disease control rate was 58.8%. Median progression‐free survival was 3.1 months (95% confidence interval 2.0–4.9). imAEs occurred in 50.0% of patients, with colitis being the most common (22.1%). Durvalumab was safely readministered to 14 patients after imAE resolution, although five experienced recurrence. Among 33 patients (48.5%) previously treated with Atez/Bev, improved responses were noted, including two partial responses. Tumor growth dynamics decreased in 60.0% of patients receiving sequential therapy. Common adverse events included elevated liver enzymes (aspartate aminotransferase 50.0%, alanine aminotransferase 48.5%), pruritus (45.6%), and rash (44.1%).ConclusionsDurvalumab plus tremelimumab therapy is feasible with proper imAE management and patient selection. Sequential treatment following Atez/Bev offers clinical benefit in advanced hepatocellular carcinoma, although some may experience rapid progression. Further biomarker research is needed to optimize immunotherapy strategies.
Intracellular tenofovir‐diphosphate concentrations in HIV pre‐exposure prophylaxis users who underwent bariatric surgery
Authors: McGarrity Matthew W. , MacPherson Paul , Li Abby , Naccarato Mark , Anderson Peter , Tan Darrell H. S. 
Published: January 2025

AbstractObjectiveTo measure concentrations of tenofovir diphosphate (TFV‐DP) in dried blood spots (DBS) among individuals taking tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC) or tenofovir alafenamide plus emtricitabine (TAF/FTC) who were scheduled to undergo or had already undergone bariatric surgery.MethodsWe enrolled pre‐exposure prophylaxis (PrEP) users attending clinics in Toronto or Ottawa who were undergoing or had undergone bariatric surgery. After participants completed a minimum of 7 days of consecutive PrEP dosing, we collected DBS samples immediately before they administered their next daily dose of PrEP. Participants who had already undergone bariatric surgery before enrolment provided a single sample at baseline only. One participant undergoing planned bariatric surgery provided samples preoperatively and on postoperative days 7, 28 and 84. TFV‐DP was measured by liquid chromatography tandem mass spectrometry. We compared results against the population range TFV‐DP at varying degrees of adherence and stratified by chronology of bariatric surgery, type of bariatric surgery and PrEP regimen.ResultsOf seven eligible participants, all were gay, cis‐gender men. Median age was 48 years (Q1–Q3: 44–51). Six participants underwent bariatric surgery before enrolment: four Roux‐en‐Y gastric bypass (RYGB) and two sleeve gastrectomy (SG). Four were taking TDF/FTC and two were taking TAF/FTC. All had therapeutic TFV‐DP concentrations, except for one TDF/FTC participant who underwent SG. One participant taking TAF/FTC enrolled before receiving RYGB and displayed a slight decrease in TFV‐DP over time, although all concentrations remained in the therapeutic range.ConclusionsTenofovir diphosphate concentrations were at or near therapeutic values in this small sample of men using oral PrEP who underwent RYGB or SG.
The employment of recommended root canal treatment procedures by dentists in Croatia and the Czech Republic
Authors: Kapitán Martin , Schmidt Jan , Vavřičková Lenka , Vidović Zdrilić Ivana , Vidas Hrstić Jelena 
Published: January 2025

AbstractAimThis study aimed to evaluate the compliance of dentists in Croatia and the Czech Republic with endodontic recommendations and identify the subjective and objective factors influencing their adherence to them.MethodologyA total of 1386 dentists from Croatia and the Czech Republic participated in an online survey through a self‐administered, author‐designed questionnaire. After excluding those who did not perform root canal treatments (RCT), 1376 responses (394 from Croatia and 982 from the Czech Republic) were statistically analysed.ResultsThe median age of respondents was 40 years, with a higher proportion of females in both countries. Croatian dentists treated fewer patients weekly but performed more RCTs and placed more composite fillings than their Czech counterparts. Czech dentists more frequently employed magnification devices, rubber dam (RD), pre‐endodontic build‐ups, nickel‐titanium (NiTi) instruments, irrigant activation, bioceramic sealers, indirect post‐endodontic restoration of lateral teeth, and single‐visit treatments. These practices were also more common among endodontists than general dental practitioners and other specialists in both countries. Croatian dentists adhered more consistently to the recommended irrigation protocol. In the Czech group, adherence to recommended procedures, such as magnification, RD usage, and irrigation protocol correlated with younger age, smaller weekly number of patients, and preference for treating patients in the supine position. No such correlations were observed among the Croatian dentists.ConclusionsDespite notable improvements in recent years, dentists still do not fully comply with the recommended RCT working procedures in Croatia and the Czech Republic.
Crop Disease Detection by Deep Joint Segmentation and Hybrid Classification Model: A CAD‐Based Agriculture Development System
Authors: Bhukya Raghuram , Vuppu Shankar , Harshvardhan A , Bukya Hanumanthu , Salendra Suresh 
Published: January 2025

ABSTRACTPrecise detection of crop disease at the early stage is a crucial task, which will reduce the spreading of disease by taking preventive measures. The main goal of this research is to propose a hybrid classification system for detecting crop disease by utilising Modified Deep Joint (MDJ) segmentation. The detection of crop diseases involves five stages. They are data acquisition, pre‐processing, segmentation, feature extraction and disease detection. In the initial stage, image data of diverse crops is gathered in the data acquisition phase. According to the work, we are considering Apple and corn crops with benchmark datasets. The input image is subjected to pre‐processing by utilising the median filtering process. Subsequently, the pre‐processed image under goes a segmentation process, where Modified Deep Joint segmentation is proposed in this work. From the segmented image, features like shape, colour, texture‐based features and Improved Median Binary Pattern (IMBP)‐based features are extracted. Finally, the extracted features are given to the hybrid classification system for identifying the crop diseases. The hybrid classification model includes Bidirectional Long Short‐Term Memory (Bi‐LSTM) and Deep Belief Network (DBN) classifiers. The outcome of both the classifiers is the score, which is subjected to an improved score level fusion model, which determines the final detection results. Finally, the performance of the proposed hybrid model is evaluated over existing methods for various metrics. At a training data of 90%, the proposed scheme attained an accuracy of 0.965, while conventional methods achieved less accuracy rates.
Autoregulation of the Master Regulator Spo0A Controls Cell‐Fate Decisions in Bacillus subtilis
Authors: Zarazúa‐Osorio Brenda , Srivastava Priyanka , Marathe Anuradha , Zahid Syeda Hira , Fujita Masaya 
Published: January 2025

ABSTRACTSpo0A in Bacillus subtilis is activated by phosphorylation (Spo0A~P) upon starvation and differentially controls a set of genes involved in biofilm formation and sporulation. The spo0A gene is transcribed by two distinct promoters, a σA‐recognized upstream promoter Pv during growth, and a σH‐recognized downstream promoter Ps during starvation, and appears to be autoregulated by four Spo0A~P binding sites (0A1‐4 boxes) localized between two promoters. However, the autoregulatory mechanisms and their impact on differentiation remain elusive. Here, we determined the relative affinity of Spo0A~P for each 0A box and dissected each promoter in combination with the systematic 0A box mutations. The data revealed that (1) the Pv and Ps promoters are on and off, respectively, under nutrient‐rich conditions without Spo0A~P, (2) the Ps promoter is activated by first 0A3 and then 0A1 during early starvation with low Spo0A~P, (3) during later starvation with high Spo0A~P, the Pv promoter is repressed by first 0A1 and then 0A2 and 0A4, and (4) during prolonged starvation, both promoters are silenced by all 0A boxes with very high Spo0A~P. Our results indicate that the autoregulation of spo0A is one of the key determinants to achieve a developmental increase in Spo0A~P, leading to a temporal window for entry into biofilm formation or sporulation.
ZjMAPKK4 Interacted With ZjNAC78 Regulates Cold Tolerance Response in Jujube
Authors: Wang Qingfang , Qi Chaofeng , Wang Linxia , Li Min , Niu Yahong , Muhammad Noor , Liu Mengjun , Liu Zhiguo , Wang Lixin 
Published: January 2025

ABSTRACTJujube (Ziziphus jujuba Mill.) holds great importance as a fruit tree in China, with strong tolerance to drought and saline stress, but its growth is limited by vulnerability to cold stress. Consequently, the role of MAPK cascades in mediating jujube cold stress response remains unclear, with the specific function of ZjMAPKK4 in this context yet to be fully elucidated. Thus, in the current study, it was found that ZjMAPKK4 was significantly upregulated compared with other ZjMAPK cascade genes after cold treatment. Heterologous transformation of ZjMAPKK4 in Arabidopsis, VIGS‐induced ZjMAPKK4 transiently silencing and overexpression of ZjMAPKK4 in jujube callus assays demonstrated that ZjMAPKK4 positively regulated the cold resistance of jujube. Furthermore, to elucidate the molecular regulation mechanism behind ZjMAPKK4 under cold stress, 25 key DEGs were screened out by transcriptome analysis. Yeast screening cDNA library, yeast two‐hybrid, LCA and Co‐IP analysis showed ZjMAPKK4 interacted with ZjNAC78 and VIGS‐induced ZjNAC78 silenced sour jujube plants showed cold sensitivity and the expression level of cold response genes were downregulated after cold stress. All the results demonstrated that ZjMAPKK4 could interact with ZjNAC78 to regulate the downstream ZjICE‐ZjCBF genes to regulate the cold tolerance of jujube.