bluuebunny/crossref_metadata_2025_split huggingface dataset:
Teclistamab impairs humoral immunity in patients with heavily pretreated myeloma: importance of immunoglobulin supplementation
Authors: Frerichs Kristine A. , Verkleij Christie P. M. , Mateos Maria Victoria , Martin Thomas G. , Rodriguez Cesar , Nooka Ajay , Banerjee Arnob , Chastain Katherine , Perales-Puchalt Alfredo , Stephenson Tara , Uhlar Clarissa , Kobos Rachel , van der Holt Bronno , Kruyswijk Sandy , Kuipers Maria T. , Groen Kaz , Vishwamitra Deeksha , Skerget Sheri , Cortes-Selva Diana , Doyle Margaret , Zaaijer Hans L. , Zweegman Sonja , Verona Raluca I. , van de Donk Niels W. C. J. 
Published: December 2023

Abstract
Teclistamab and other B-cell maturation antigen (BCMA)–targeting bispecific antibodies (BsAbs) have substantial activity in patients with heavily pretreated multiple myeloma (MM) but are associated with a high rate of infections. BCMA is also expressed on normal plasma cells and mature B cells, which are essential for the generation of a humoral immune response. The aim of this study was to improve the understanding of the impact of BCMA-targeting BsAbs on humoral immunity. The impact of teclistamab on polyclonal immunoglobulins and B cell counts was evaluated in patients with MM who received once-weekly teclistamab 1.5 mg/kg subcutaneously. Vaccination responses were assessed in a subset of patients. Teclistamabinduced rapid depletion of peripheral blood B cells in patients with MM and eliminated normal plasma cells in ex vivo assays. In addition, teclistamab reduced the levels of polyclonal immunoglobulins (immunoglobulin G [IgG], IgA, IgE, and IgM), without recovery over time while receiving teclistamab therapy. Furthermore, response to vaccines against Streptococcus pneumoniae, Haemophilus influenzae type B, and severe acute respiratory syndrome coronavirus 2 was severely impaired in patients treated with teclistamab compared with vaccination responses observed in patients with newly diagnosed MM or relapsed/refractory MM. Intravenous immunoglobulin (IVIG) use was associated with a significantly lower risk of serious infections among patients treated with teclistamab (cumulative incidence of infections at 6 months: 5.3% with IVIG vs 54.8% with observation only [P &lt; .001]). In conclusion, our data show severe defects in humoral immunity induced by teclistamab, the impact of which can be mitigated by the use of immunoglobulin supplementation. This trial was registered at www.ClinicalTrials.gov as #NCT04557098.
Competing treatments for migraine: a headache for decision-makers
Authors: Mistry Hema , Naghdi Seyran , Underwood Martin , Duncan Callum , Madan Jason , Matharu Manjit 
Published: December 2023

Abstract
Background
Migraine is the world’s second most common disabling disorder, affecting 15% of UK adults and costing the UK over £1.5 billion per year. Several costly new drugs have been approved by National Institute for Health and Care Excellence.

Aim
To assess the cost-effectiveness of drugs used to treat adults with chronic migraine.

Methods
We did a systematic review of placebo-controlled trials of preventive drugs for chronic migraine. We then assessed the cost-effectiveness of the currently prescribable drugs included in the review: Onabotulinum toxin A (BTA), Eptinezumab (100mg or 300mg), Fremanezumab (monthly or quarterly dose), Galcanezumab or Topiramate, each compared to placebo, and we evaluated them jointly. We developed a Markov (state-transition) model with a three-month cycle length to estimate the costs and quality-adjusted life years (QALYs) for the different medications from a UK NHS and Personal Social Services perspective. We used a two-year time horizon with a starting age of 30 years for the patient cohort. We estimated transition probabilities based on monthly headache days using a network meta-analysis (NMA) developed by us, and from published literature. We obtained costs from published sources and applied discount rates of 3.5% to both costs and outcomes.

Results
Deterministic results suggest Topiramate was the least costly option and generated slightly more QALYs than the placebo, whereas Eptinezumab 300mg was the more costly option and generated the most QALYs. After excluding dominated options, the incremental cost-effectiveness ratio (ICER) between BTA and Topiramate was £68,000 per QALY gained and the ICER between Eptinezumab 300mg and BTA was not within plausible cost-effectiveness thresholds. The cost-effectiveness acceptability frontier showed that Topiramate is the most cost-effective medication for any amount the decision maker is willing-to-pay per QALY.

Conclusions
Among the various prophylactic medications for managing chronic migraine, only Topiramate was within typical cost-effectiveness threshold ranges. Further research is needed, ideally an economic evaluation alongside a randomised trial, to compare these newer, expensive CGRP MAbs with the cheaper oral medications.
What to do with non-responders to CGRP(r) monoclonal antibodies: switch to another or move to gepants?
Authors: Waliszewska-Prosół Marta , Vuralli Doga , Martelletti Paolo 
Published: December 2023

AbstractIn this editorial we aim to provide potential therapeutic options in patients who do not benefit from treatment with CGRP(r) monoclonal antibodies. Based on current real-life studies and analysis of practical and economic aspects, we will analyze the potential benefits of changing CGRP-targeted treatment.
The implementation of the substitution principle in European chemical legislation: a comparative analysis
Authors: Slunge Daniel , Miguel Mécia , Lindahl Lina , Backhaus Thomas 
Published: December 2023

Abstract
Background
The substitution of hazardous chemicals with safer alternatives is an important objective in European chemical policy, but implementation has been slower than expected. We conduct a comprehensive analysis and comparison of the implementation of the substitution principle in European regulations for pesticides, biocides, and industrial chemicals. Specifically, we examine and compare the criteria and processes associated with the identification of candidates for substitution and the assessment of alternatives.

Results
We find only minor differences in the criteria applied to identify candidates for substitution amongst pesticides, biocides, and industrial chemicals, but larger differences concerning the processes used. While all substances that are to be approved as a pesticide and biocide are systematically evaluated against the established criteria for substitution, the substitution process for industrial chemicals only focuses on those substances identified as substances of very high concern. The main reason candidates for substitution remain on the market is the lack of identified safer chemical alternatives and the insufficient consideration of non-chemical alternatives, caused, at least to a large extent, by the comparatively weak incentives provided by current regulations.

Conclusions
The systematic approach for the identification of industrial substances of very high concern (SVHC) under ECHAs “Integrated Regulatory Strategy” is much welcome. However, no final conclusion on SVHC properties or the need for regulatory action has been drawn for approximately 90% of the REACH-registered substances, as often even basic hazard and exposure data are missing. Hence, at least a screening-level evaluation of SVHC properties should become a mandatory part of the substance registration under REACH. To reduce the risk of strategic behaviour in the search for alternatives to industrial chemicals identified as SVHC, a setup in which regulatory authorities play a larger role as information and knowledge brokers should be considered. Investments in innovation as well as improved sharing of information and a better distribution of the workloads amongst European authorities might also improve the identification of safer alternatives. However, without stronger incentives, making it more costly for companies to continue using hazardous substances relative to safer alternatives, initiatives to promote substitution are likely to have limited success.
Daily intake of 30 mg duloxetine is effective in decreasing premature ejaculation severity: a prospective randomized placebo-controlled cross over clinical trial
Authors: Zaazaa Adham , Nasr Eldin Mohamed , GamalEl Din Sameh Fayek , Zeidan Ashraf , Saleh Mohamed Yassin Mohamed , Adel Ahmed , Shokr Mohamed 
Published: December 2023

Abstract
Background
Premature ejaculation (PE) is considered to be the most common male sexual disorder affecting 20% to 66% of sexually active men. Most of the patients had already tried on demand dapoxitine with no improvement. We aimed in the current study to assert the efficacy and safety profile of daily intake of 30 mg duloxetine in treating patients with lifelong premature ejaculation (LPE) as well as patients with acquired premature ejaculation (APE).

Results
The current study showed significant improvement in intravaginal ejaculatory latency time (IELT) after intake of duloxetine. All participants had a median Arabic index of premature ejaculation (AIPE) of 26, median IELT of 180 s, median male sexual quality of life (SQOL) of 43 after being treated with duloxetine (p value < 0.001 for all). While median AIPE after placebo was 19, median IELT after placebo was 60 s and median male SQOL after placebo was 21. Paired comparison of AIPE, IELT (Secs), inter quartile range (IQR) and male SQOL in group (A) patients at baseline and after duloxetine intake showed statistically significant improvement among treated patients (p values < 0.001 for all). Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (A) patients at baseline and after placebo treatment showed no significant improvement of male SQOL. Furthermore, AIPE and IELT returned to baseline scores after discontinuation of duloxetine (p values 0.729; 0.892, respectively). Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (B) patients at baseline and after placebo treatment showed almost same scores of patients in group (A) who received placebo for 2 months after a 2 month washout period (p values 1.000 for all).
Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (B) patients at baseline and after duloxetine treatment showed statistically significant improvement among all treated patients (p values < 0.001 for all).

Conclusion
Duloxetine is an effective drug for treatment of LPE and APE patients. Further, larger studies are needed to compare duloxetine to different known therapeutic modalities for PE to assert it’s efficacy and superiority.
Association between opioid abuse and COVID-19 susceptibility: a propensity score matched study
Authors: Hedayatyaghoobi Mojtaba , Azizmohammad Looha Mehdi , Shafiee Arman , Jafarabady Kyana , Safari Omid , Alirezaei Amirhesam , Bakhtiyari Mahmood 
Published: December 2023

Abstract
Background
Opioid use disorder (OUD) has been associated with adverse health outcomes, and its potential impact on COVID-19 outcomes is of significant concern. This study aimed to assess the susceptibility and clinical outcomes of hospitalized COVID-19 patients with OUD using a propensity score-matched design.

Methods
A historical cohort study was conducted in Alborz province, Iran, during the early months of the COVID-19 pandemic. Patients aged 18 years and above with confirmed COVID-19 were included in the study. OUD was defined as a compulsive urge to use opioids or opioid-derivative drugs. Non-opioid abusers with COVID-19 were selected as the control group. Data on demographics, clinical characteristics, laboratory factors, comorbidities, and vital signs were collected. Propensity score matching (PSM) was used to balance the groups and assess the impact of OUD on ICU admission, mortality, the need for intubation, and the severity of pulmonary involvement on CT scans.

Results
A total of 442 patients were included in the study, with 351 discharged and 34 deceased. The PSM analysis showed that OUD was not significantly associated with ICU admission (OR: 1.87, 95% CI: 0.22–2.91, p = 0.631). However, opium users had an increased risk of mortality (OR: 2.38, 95% CI: 1.30–4.35, p = 0.005) and a higher likelihood of requiring intubation (OR: 3.57, 95% CI: 1.38–9.39, p = 0.009) compared to non-opioid abusers. The severity of pulmonary involvement on CT scans did not show a significant association with OUD.

Conclusion
OUD among hospitalized COVID-19 patients was associated with an increased risk of mortality and the need for intubation. These findings highlight the importance of addressing OUD as a potential risk factor in the management and treatment of COVID-19 patients. Further research is warranted to explore the underlying mechanisms and develop appropriate interventions to mitigate the impact of OUD on COVID-19 outcomes.
The diagnostic dilemma for atypical presentation of progressive human Mpox
Authors: Sahra Syeda , Villalobos Raul Orozco , Scott Brian M. , Bowman Deidra J. , Sassine Joseph , Salvaggio Michelle , Drevets Douglas A. , Higuita Nelson Iván Agudelo 
Published: December 2023

Abstract
Background
Human mpox has increasingly been reported worldwide since May 2022, with higher incidence in men who have sex with men (MSM) and persons living with HIV (PLHIV) with presentation typical for generalized macules and papules.

Case presentation
We are describing a case of human mpox, which presented as widespread, atypical round verrucous lesions that went undiagnosed in the community for six months and was treated with antibacterials and antifungals given the similarity to skin manifestations associated with endemic mycoses.

Conclusions
Suspicion for human mpox should be high in young MSM and PLHIV who present with rash and mpox should be ruled out earlier.
Correlation between gut microbiome and cognitive impairment in patients undergoing peritoneal dialysis
Authors: Wang Jingjing , Wu Siyang , Zhang Jin , Li Yuanyuan , Wu Yonggui , Qi Xiangming 
Published: December 2023

Abstract
Background
Growing evidence has demonstrated that patients undergoing peritoneal dialysis (PD) are more likely to experience cognitive impairment than patients with non-dialysis end-stage renal disease (ESRD); however, the underlying mechanisms remain unclear. This study aimed to identify the role and predictive significance of gut microbiome alterations in PD-associated cognitive impairment.

Methods
A total of 29 non-dialysis ESRD patients and 28 PD patients were enrolled in this study and divided into subgroups according to the Montreal Cognitive Assessment (MoCA). Faecal samples were analyzed using 16 S rRNA. Mini-Mental State Examination (MMSE) and MoCA scores were used to assess the degree of cognitive impairment in patients.

Results
The 16 S rRNA analysis demonstrated differences in gut microbiome abundance and structure between PD and non-dialysis ESRD patients and between PD patients with cognitive impairment (PCI) and PD patients with normal cognition (PNCI). At family and genus levels, Prevotellaceae exhibited the greatest structure difference, while Lactobacillus exhibited the greatest abundance difference between PCI and PNCI. Altered microbiota abundance significantly correlated with cognitive function and serum indicators in PD. In addition, different modules related to fatty acid, lipid, pantothenate, and coenzyme A biosynthesis, and tyrosine and tryptophan metabolism were inferred from 16 S rRNA data between PCI and PNCI. Both groups could be distinguished using models based on the abundance of Lactobacillaceae (Area under curve [AUC] = 0.83), Actinomycetaceae (AUC = 0.798), and Prevotellaceae (AUC = 0.778) families and Lactobacillus (AUC = 0.848) and Actinomyces (AUC = 0.798) genera.

Conclusion
Gut microbiome evaluation could aid early cognitive impairment diagnosis in patients undergoing PD.
Association between composite dietary antioxidant index and coronary heart disease among US adults: a cross-sectional analysis
Authors: Ma Ruicong , Zhou Xinyang , Zhang Guolin , Wu Hongying , Lu Yi , Liu Fengyi , Chang Yeting , Ding Yanchun 
Published: December 2023

Abstract
Background
The Composite Dietary Antioxidant Index (CDAI) is a dietary antioxidant score that plays a protective role in many diseases, including depression, osteoporosis, papillomavirus infection, etc. However, the association between CDAI and coronary heart disease (CHD) is currently unclear. We aim to explore the correlations between CDAI and the risk of CHD.

Methods
Eligible participants were obtained from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. All participants in this cross-sectional study are required to undergo two separate 24-h dietary recall interviews. Average daily intakes of dietary antioxidants were used to calculate CDAI. CHD status was determined through a questionnaire. Weighted multiple logistic regression models were used to evaluate the relationship between CDAI and CHD. Moreover, we also used restricted cubic spline to explore Non-linear correlations. Sensitivity analysis using unweighted logistic analysis and subgroup analysis were used to demonstrate the stability of the results.

Results
A total of 34,699 participants were eligible for analysis.Compared to the participants without CHD, the participants with CHD showed lower levels of CDAI. After adjusting confounding factors in the multivariate weighted logistic regression model, CDAI was inversely associated with CHD (Q4 vs. Q1, OR = 0.65 (0.51–0.82, P < 0.001). Restricted cubic spline showed that there was a negative non-linear correlation (L-shaped) between CDAI and CHD, suggesting a potential saturation effect at higher CDAI levels, with the inflection point of 0.16. Sensitivity analysis showed that the results were stable. No significant statistically interaction was showed in subgroup analysis.

Conclusions
There was a negative non-linear correlation between CDAI and CHD in US adults. However, further prospective studies are still needed to reveal their relationship.
Development and validation of two nomograms for predicting overall survival and Cancer-specific survival in prostate cancer patients with bone metastases: a population-based study
Authors: Li Baochao , Xing Jiajun , Wang Zhongyuan , Gong Zixuan , Wang Zengjun , Xu Aiming 
Published: December 2023

Abstract
Background
Prostate cancer with bone metastasis has significant invasiveness and markedly poorer prognosis. The purpose of this study is to establish two nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) of prostate cancer patients with bone metastasis.

Methods
From January 2000 to December 2018, a total of 2683 prostate adenocarcinoma with bone metastasis patients were identified from the Surveillance, Epidemiology, and End Results Program (SEER) database. These patients were then divided into a training cohort and a validation cohort, with OS and CSS as the study endpoints. Correlation analyses were employed to assess the relationship between variables. Univariate and multivariate Cox analyses were utilized to ascertain the independent prognostic factors. Calibration curves and the area under the time-dependent receiver operating characteristic curve (time-dependent AUC) were employed to evaluate discrimination and calibration of the nomogram. DCA was applied to examine accuracy and clinical benefits. The clinical utility of the nomogram and the AJCC Stage System was compared using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Lastly, the risk stratifications of the nomogram and the AJCC Stage System were compared.

Results
There was no collinearity among the variables that were screened. The results of multivariate Cox regression analysis showed that seven variables (age, surgery, brain metastasis, liver metastasis, lung metastasis, Gleason score, marital status) and six variables (age, surgery, lung metastasis, liver metastasis, Gleason score, marital status) were identified to establish the nomogram for OS and CSS, respectively. The calibration curves, time-dependent AUC curves, and DCA revealed that both nomograms had pleasant predictive power. Furthermore, NRI and IDI confirmed that the nomogram outperformed the AJCC Stage System.

Conclusion
Both nomograms had satisfactory accuracy and were validated to assist clinicians in evaluating the prognosis of PABM patients.
Change in surface properties of two different dental resin composites after using various beverages and brushing
Authors: Elmalawany Lamia M. , El-Refai Dina A. , Alian Ghada A. 
Published: December 2023

Abstract
Background
The study aimed to evaluate the influence of various beverages; with and without brushing; on the surface mechanical properties of two resin composites.

Methods
A total of 160 disc-shaped specimens were prepared for each of the following dental composites; nanohybrid ormocer (Admira fusion, VOCO GmbH, Cuxhaven, Germany) and nanohybrid resin composite (Grandio, VOCO GmbH, Cuxhaven, Germany). The baseline surface hardness and roughness measurements were carried out after 24 h. The composite samples were randomly distributed into one of the two groups; brushing and non-brushing, which were further divided into one of the four subgroups (n = 10); artificial saliva as control, coffee, red wine, and soft drink. In the non-brushing group, the specimens were immersed in the different beverages for five minutes three times daily for 30 days. The same procedure was done for the brushing group, in addition to brushing the specimens for five seconds. The surface hardness and roughness measurements were repeated after 30 days. One-way ANOVA and independent t-tests were used for statistical analysis.

Results
The soft drink had the most deteriorating effect and artificial saliva had the least. The change in surface properties was higher in the brushing subgroups. Grandio exhibited a higher change in surface microhardness while Admira fusion exhibited a higher change in surface roughness.

Conclusions
The surface properties of both dental resin composites were negatively affected by using beverages and brushing.