bluuebunny/crossref_metadata_2025_split huggingface dataset:
DBSegment: Fast and robust segmentation of deep brain structures considering domain generalization
Authors: Baniasadi Mehri , Petersen Mikkel V. , Gonçalves Jorge , Horn Andreas , Vlasov Vanja , Hertel Frank , Husch Andreas 
Published: October 2022

AbstractSegmenting deep brain structures from magnetic resonance images is important for patient diagnosis, surgical planning, and research. Most current state‐of‐the‐art solutions follow a segmentation‐by‐registration approach, where subject magnetic resonance imaging (MRIs) are mapped to a template with well‐defined segmentations. However, registration‐based pipelines are time‐consuming, thus, limiting their clinical use. This paper uses deep learning to provide a one‐step, robust, and efficient deep brain segmentation solution directly in the native space. The method consists of a preprocessing step to conform all MRI images to the same orientation, followed by a convolutional neural network using the nnU‐Net framework. We use a total of 14 datasets from both research and clinical collections. Of these, seven were used for training and validation and seven were retained for testing. We trained the network to segment 30 deep brain structures, as well as a brain mask, using labels generated from a registration‐based approach. We evaluated the generalizability of the network by performing a leave‐one‐dataset‐out cross‐validation, and independent testing on unseen datasets. Furthermore, we assessed cross‐domain transportability by evaluating the results separately on different domains. We achieved an average dice score similarity of 0.89 ± 0.04 on the test datasets when compared to the registration‐based gold standard. On our test system, the computation time decreased from 43 min for a reference registration‐based pipeline to 1.3 min. Our proposed method is fast, robust, and generalizes with high reliability. It can be extended to the segmentation of other brain structures. It is publicly available on GitHub, and as a pip package for convenient usage.
Amplitude modulating frequency overrides carrier frequency in tACS‐induced phosphene percept
Authors: Hsu Che‐Yi , Liu Tzu‐Ling , Lee Dong‐Han , Yeh Ding‐Ruey , Chen Yan‐Hsun , Liang Wei‐Kuang , Juan Chi‐Hung 
Published: October 2022

AbstractThe amplitude modulated (AM) neural oscillation is an essential feature of neural dynamics to coordinate distant brain areas. The AM transcranial alternating current stimulation (tACS) has recently been adopted to examine various cognitive functions, but its neural mechanism remains unclear. The current study utilized the phosphene phenomenon to investigate whether, in an AM‐tACS, the AM frequency could modulate or even override the carrier frequency in phosphene percept. We measured the phosphene threshold and the perceived flash rate/pattern from 12 human subjects (four females, aged from 20–44 years old) under tACS that paired carrier waves (10, 14, 18, 22 Hz) with different envelope conditions (0, 2, 4 Hz) over the mid‐occipital and left facial areas. We also examined the phosphene source by adopting a high‐density stimulation montage. Our results revealed that (1) phosphene threshold was higher for AM‐tACS than sinusoidal tACS and demonstrated different carrier frequency functions in two stimulation montages. (2) AM‐tACS slowed down the phosphene flashing and abolished the relation between the carrier frequency and flash percept in sinusoidal tACS. This effect was independent of the intensity change of the stimulation. (3) Left facial stimulation elicited phosphene in the upper‐left visual field, while occipital stimulation elicited equally distributed phosphene. (4) The near‐eye electrodermal activity (EDA) measured under the threshold‐level occipital tACS was greater than the lowest power sufficient to elicit retinal phosphene. Our results show that AM frequency may override the carrier frequency and determine the perceived flashing frequency of AM‐tACS‐induced phosphene.
Pilot randomized, controlled, preoperative intervention for nutrition trial in head and neck cancer
Authors: Sykes Kevin J. , Gibbs Heather , Farrokhian Nathan , Arthur Anna , Flynn John , Shnayder Yelizaveta , Kakarala Kiran , Nallani Rohit , Smith Joshua B. , Penn Joseph , Fassas Scott , Cummings Emily , Arambula Zack , Karadaghy Omar , Bur Andrés M. 
Published: October 2022

AbstractBackgroundSeveral prospective studies report improved outcomes with pretreatment nutrition interventions prior to radiation therapy for head and neck cancer (HNC), but none have assessed similar interventions before surgery for HNC.MethodsPOINT, a pilot randomized controlled trial, was conducted to evaluate a multimodal nutrition intervention. Patients undergoing primary surgery with free flap reconstruction for HNC were randomly assigned to the control arm or a preoperative multimodal nutrition intervention.ResultsPOINT included 49 patients. Nutrition risk scores did not change significantly for either the intervention or control group. Control patients had a significant decrease in body weight in the preoperative period (p < 0.001). Conversely, weight among intervention patients did not significantly decrease (p = 0.680). The intervention mitigated weight loss in patients with dysphagia (p = 0.001).ConclusionsPreoperative nutrition optimization shows potential to reduce weight loss normally experienced by patients with head and neck cancer prior to surgical extirpation, especially among those with subjective dysphagia.
Management of patients with lymphoma and COVID‐19: Narrative review and evidence‐based practical recommendations
Authors: Passamonti Francesco , Nicastri Emanuele , Di Rocco Alice , Guarini Attilio , Ibatici Adalberto , Luminari Stefano , Mikulska Malgorzata , Visco Carlo 
Published: October 2022

AbstractPatients with hematologic malignancies can be immunocompromized because of their disease, anti‐cancer therapy, and concomitant immunosuppressive treatment. Furthermore, these patients are usually older than 60 years and have comorbidities. For all these reasons they are highly vulnerable to infection with severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) and have an increased risk of developing severe/critical Coronavirus disease 2019 (COVID‐19) compared to the general population. Although COVID‐19 vaccination has proven effective in reducing the incidence of severe/critical disease, vaccinated patients with lymphoma may not be protected as they often fail to develop a sufficient antiviral immune response. There is therefore an urgent need to address the management of patients with lymphoma and COVID‐19 in the setting of the ongoing pandemic. Passive immunization with monoclonal antibodies against SARS‐CoV‐2 is a currently available complementary drug strategy to active vaccination for lymphoma patients, while monoclonal antibodies and antiviral drugs (remdesivir, ritonavir‐boosted nirmatrelvir, and molnupiravir) have proven effective in preventing the progression to severe/critical COVID‐19. In this narrative review we present the most recent data documenting the characteristics and outcomes of patients with concomitant lymphoma and COVID‐19. Our ultimate goal is to provide practice‐oriented guidance in the management of these vulnerable patients from diagnosis to treatment and follow‐up of lymphoma. To this purpose, we will first provide an overview of the main data concerning prognostic factors and fatality rate of lymphoma patients who develop COVID‐19; the outcomes of COVID‐19 vaccination will also be addressed. We will then discuss current COVID‐19 prophylaxis and treatment options for lymphoma patients. Finally, based on the literature and our multidisciplinary experience, we will summarize a set of indications on how to manage patients with lymphoma according to COVID‐19 exposure, level of disease severity and former history of infection, as typically encountered in clinical practice.
A phase 1/2, open‐label, multicenter study of isatuximab in combination with cemiplimab in patients with lymphoma
Authors: Carlo‐Stella Carmelo , Zinzani Pier Luigi , Sureda Anna , Araújo Luis , Casasnovas Olivier , Carpio Cecilia , Yeh Su‐Peng , Bouabdallah Krimo , Cartron Guillaume , Kim Won Seog , Cordoba Raul , Koh Youngil , Re Alessandro , Alves Daniela , Chamuleau Martine , Le Gouill Steven , López‐Guillermo Armando , Moreira Ilídia , van der Poel Marjolein W. M. , Abbadessa Giovanni , Meng Robin , Ji Ran , Lépine Lucie , Saleem Rao , Ribrag Vincent 
Published: October 2022

AbstractPatients with relapsed or refractory lymphoma have limited treatment options, requiring newer regimens. In this Phase 1/2 study (NCT03769181), we assessed the safety, efficacy, and pharmacokinetics of isatuximab (Isa, anti‐CD38 antibody) in combination with cemiplimab (Cemi, anti‐programmed death‐1 [PD‐1] receptor antibody; Isa + Cemi) in patients with classic Hodgkin lymphoma (cHL), diffuse large B‐cell lymphoma (DLBCL), and peripheral T‐cell lymphoma (PTCL). In Phase 1, we characterized the safety and tolerability of Isa + Cemi with planned dose de‐escalation to determine the recommended Phase 2 dose (RP2D). Six patients in each cohort were treated with a starting dose of Isa + Cemi to determine the RP2D. In Phase 2, the primary endpoints were complete response in Cohort A1 (cHL anti‐PD‐1/programmed death‐ligand 1 [PD‐L1] naïve), and objective response rate in Cohorts A2 (cHL anti‐PD‐1/PD‐L1 progressors), B (DLBCL), and C (PTCL). An interim analysis was performed when the first 18 (Cohort A1), 12 (Cohort A2), 17 (Cohort B), and 11 (Cohort C) patients in Phase 2 had been treated and followed up for 24 weeks. Isa + Cemi demonstrated a manageable safety profile with no new safety signals. No dose‐limiting toxicities were observed at the starting dose; thus, the starting dose of each drug was confirmed as the RP2D. Based on the Lugano 2014 criteria, 55.6% (Cohort A1), 33.3% (Cohort A2), 5.9% (Cohort B), and 9.1% (Cohort C) of patients achieved a complete or partial response. Pharmacokinetic analyses suggested no effect of Cemi on Isa exposure. Modest clinical efficacy was observed in patients with cHL regardless of prior anti‐PD‐1/PD‐L1 exposure. In DLBCL or PTCL cohorts, interim efficacy analysis results did not meet prespecified criteria to continue enrollment in Phase 2 Stage 2. Isa + Cemi did not have a synergistic effect in these patient populations.
Challenges faced by African healthcare workers during the third wave of the pandemic
Authors: Nchasi Goodluck , Okonji Osaretin Christabel , Jena Rahul , Ahmad Shahzaib , Soomro Umar , Kolawole Barakat Olajumoke , Nawaz Faisal A. , Essar Mohammad Yasir , Aborode Abdullahi Tunde 
Published: October 2022

AbstractAfrica experienced the third wave of the coronavirus disease in 2019, which caused an 18% rise in cases in most parts of the continent. As of January 2022, the region had an estimated 10.4 million cumulative cases and more than 233,000 deaths, which add up to the burden on the fragile healthcare system, which continues to face a shortage of staff and resources. In addition, the progression of the pandemic further threatens the supply of healthcare workers in Africa due to the increased risk of infection and death, where more than 10,000 healthcare workers in 40 countries have been infected with the virus. This is amid low vaccination coverage, with only 27% of healthcare workers in Africa being fully vaccinated against the disease. Despite the delayed start and slow progression of the pandemic in Africa, there are increasing concerns over the challenges on the African healthcare workers such as economic insecurity and stressful working conditions, which are associated with limited access to personal protective equipment and other vital resources such as ventilators. In addition, the pandemic further predisposes African healthcare workers to social stigma, burnout, insomnia, depression, and fear of safety in their families. The aim of this study is to highlight the challenges faced by African healthcare workers, provide recommendations for change, and emphasize the need to prioritize their physical and mental well‐being.
Mutation of theTP53gene in acute lymphoblastic leukemia does not affect survival outcomes after haploidentical hematopoietic stem cell transplantation
Authors: Zhou Cuiyan , Zheng Fengmei , Xu Lanping , Zhang Xiaohui , Chang Yingjun , Mo Xiaodong , Sun Yuqian , Huang Xiaojun , Wang Yu 
Published: October 2022

AbstractPrevious studies have demonstrated that TP53 mutation is correlated with insufficient therapy response and unfavorable prognosis in acute lymphoblastic leukemia (ALL). Few studies have investigated the impact of TP53 mutation in ALL patients after haploidentical hematopoietic stem cell transplantation (haplo‐HSCT). We completed a retrospective study of 65 ALL patients with available TP53 status who underwent haplo‐HSCT. They were divided into a TP53 mutation group (TP53mut) and a TP53 wild‐type (TP53wt) group. TP53mutshowed comparable 2‐year cumulative incidence of relapse (CIR) rates (13.1% vs 12.5%,P = .96) and 2‐year leukemia‐free survival (LFS) (74.2% vs 77.4%,P = .80) with TP53wt. No significant differences in 2‐year overall survival (OS) rates (82.9% vs 87.3%,P = .61) or 2‐year NRM rates (12.7% vs 10.2%,P = .69) were observed in TP53mutand TP53wtpatients. Multivariate analysis suggested that white blood cell (WBC) count at initial diagnosis (>50 × 109/L: hazard ratio [HR] = 3.860,P = .016) and age (>40 years old: HR = 4.120,P = .012) are independent risk factors for 2‐year LFS. Our study showed that TP53 mutations may not be related to the unfavorable impact on survival in ALL patients after treatment with haplo‐HSCT. The present results suggested that haplo‐HSCT may eliminate the poor prognosis effect of TP53 mutation in ALL.
Ethical commitment, institutional investors and financial performance: Malaysian evidence
Authors: Zainul Abidin Ahmad Firdhauz , Hashim Hafiza Aishah , Ariff Akmalia Mohamad , Al‐ahdal Waleed M. 
Published: October 2022

AbstractThis study investigates whether institutional investors moderate the relationship between ethical commitment and financial performance amongst Malaysian companies. Through the role of institutional investors, the external monitoring mechanism is expected to reduce the cost associated with the agency problem amongst Malaysian companies, as shown by the lack of ethical practises. Using data from 429 publicly listed companies on the Main Board of Bursa Malaysia from 2012 to 2021, the results show that companies with higher ETHICS have better financial performance than companies with lower ETHICS. However, the findings on the moderating effect of institutional investors cannot be proven. By separating the sample based on pre‐MCCG 2017, institutional investors were found to have an association between ETHICS and performance, but no evidence was found during the period post‐MCCG 2017. This study adds to the perspective of agency theory in the academic literature, of which companies can create values by being committed to higher ethical practises. Results on the moderating effect of institutional investors provide perspective on external monitoring mechanisms in the Malaysian market because they are found to have a monitoring role in enhancing corporate performance. However, such a role decreases after the introduction of MCCG 2017. This study provides insights for Malaysian regulators on the necessity to keep promoting ethical practises and transparency amongst companies to achieve the goals of the National Anti‐Corruption Plan 2019–2023. The ethical practises, however, are not limited to listed companies, and regulators should also consider monitoring the institutions within the capital market.
Associations of dispositional forgivingness with facets of well‐being among Colombian adults: A longitudinal outcome‐wide analysis
Authors: Cowden Richard G. , Chen Zhuo Job , Bechara Andrea Ortega , Worthington Everett L. 
Published: October 2022

Many studies have reported evidence suggesting that dispositional forgivingness has positive implications for different domains of well‐being. However, relatively few methodologically rigorous studies have been conducted in the Global South, particularly in post‐conflict settings where forgiveness could play an important role in supporting individual well‐being. In this three‐wave cohort study of predominantly young adult Colombians (n = 1575), we examined the associations of dispositional forgivingness with 20 well‐being outcomes across several domains of well‐being: psychological distress, psychological well‐being, physical health, social well‐being, and character strengths/virtues. Using an outcome‐wide analytic design that included extensive control for potential confounding and reverse causation by adjusting for a range of covariates assessed in Wave 1 (2017), we found that dispositional forgivingness assessed in Wave 2 (2018) was at least modestly associated with improvements in one or more facet of each well‐being domain assessed approximately 1 year later in Wave 3 (2019). Associations tended to be stronger for outcomes in the domains of psychological distress, psychological well‐being, social well‐being, and character strengths/virtues compared to the physical health domain. These longitudinal findings suggest that dispositional forgivingness might promote individual well‐being in societies with a long history of ongoing civil unrest, conflict, and war.
Silencing of lncRNA KLF3‐AS1 represses cell growth in osteosarcoma via miR‐338‐3p/MEF2C axis
Authors: Chen Chunfa , Liu Liang 
Published: October 2022

AbstractBackgroundOsteosarcoma (OS) is a highly recurrent malignancy occurring among adolescents. The goal of this research was to scrutinize the role and action mechanism of KLF3‐AS1 in OS.MethodsWestern blotting and quantitative reverse transcription real‐time PCR were conducted to ascertain the mRNA expressions of miR‐338‐3p, KLF3‐AS1, and MEF2C in OS cell lines and tissue samples. Colony formation and CCK‐8 experiments were done to evaluate the proliferative capacity of the cells. Western blotting was also executed to measure the relative expressions of the proteins Bcl‐2 and Bax. RNA immunoprecipitation and dual luciferase reporter experiments were carried out to validate the target relationships among MEF2C, KLF3‐AS1, and miR‐338‐3p. Mouse xenograft models were created to assess the influences of KLF3‐AS1 on the growth of tumors in vivo.ResultsElevated levels of KLF3‐AS1 and MEF2C and reduced amounts of miR‐338‐3p were identified in OS. KLF3‐AS1 targeted miR‐338‐3p, and miR‐338‐3p further targeted MEF2C. Silencing KLF3‐AS1 induced apoptosis and attenuated proliferation in vitro and repressed the tumor growth in vivo. Inhibiting miR‐338‐3p inverted the cancer‐suppressing effects of KLF3‐AS1 silencing. Meanwhile, loss of MEF2C partially eliminated the effects brought about by miR‐338‐3p downregulation, namely the stimulation of cell growth and suppression of apoptosis.ConclusionsSilencing of KLF3‐AS1 could repress the growth of cells and induce apoptosis by regulating miR‐338‐3p/MEF2C in OS. This suggests that the regulatory axis KLF3‐AS1/miR‐338‐3p/MEF2C is a prospective target for OS treatment.
A high‐resolution monitoring station for the in situ assessment of nitrate‐related redox processes at an agricultural site
Authors: Richard‐Cerda Juan Carlos , Giber Alexandra , Muñoz‐Vega Edinsson , Kübeck Christine , Berthold Georg , Schüth Christoph , Schulz Stephan 
Published: October 2022

AbstractBiogeochemical redox processes control the chemical behavior of many major and trace elements, making their comprehension crucial for predicting and protecting environmental health. Nitrogen (N) is especially susceptible to changes in soil redox conditions and affects the cycles of other redox‐sensitive species. Elevated N concentrations, in nitrate form, in agricultural soils and associated freshwater ecosystems constitute a problem in many parts of the world. Although a wide variety of measures have been adopted, their assessment through concentration measurements in groundwater and surface water of the different monitoring networks has shortcomings. Nitrate, as a non‐point pollutant, is subject to several processes (e.g., transformation and retardation) before it is detected, making it impossible to evaluate measurements’ effectiveness reliably. Thus, we designed and constructed a monitoring station featuring commercially available products and self‐manufactured components at an agricultural site for the in situ assessment of nitrate‐related processes by high‐resolution monitoring of hydraulic (soil water content, matric potential, groundwater head) and hydrogeochemical variables (oxidation‐reduction potential and groundwater and pore water chemistry) within the vadose zone and the shallow aquifer. The monitoring station has proven to be a reliable tool. Changes over depth and time of measured variables have been identified, allowing the detection of the transient behavior of the redox reactive zone and the interpretation of ongoing denitrification processes and other redox nitrate‐triggered phenomena, such as uranium roll‐front and selenium accumulation at the redox interface. Measuring both geochemical and soil water variables allows for the calculation of in situ solute inputs into the groundwater and their reaction rates.
Australian healthcare professionals' perspectives on the ethical and practical issues associated with genomic newborn screening
Authors: Cao Michelle , Notini Lauren , Ayres Samantha , Vears Danya F. 
Published: October 2022

AbstractNewborn bloodspot screening (NBS) is a successful public health initiative that seeks to identify serious, treatable medical conditions. The increasing use of genomic sequencing (GS) in a wide range of medical settings has reignited the discussion on whether GS can and should be integrated into NBS. Yet, the perspectives of healthcare professionals (HCPs) in Australia on the ethical and practical issues associated with the implementation of genomic newborn screening (GNBS) are underexplored. To address this, we conducted semi‐structured interviews with 16 Australian HCPs with clinical or policy experience in NBS and/or GS to explore their perspectives on the ethical, social, and practical issues raised by integrating GS into NBS. Interviews were analyzed using inductive content analysis. When asked whether GS should be incorporated into NBS, HCPs did not feel it was currently appropriate but there was a strong consensus it may be implemented within the next decade. However, HCPs had differing perspectives on what conditions should be included and how to best handle the volume of data generated from GNBS. Our findings have important implications for determining at what point and how genomics can be integrated into NBS. The differing views expressed amongst HCPs suggest that further research is needed to explore the reasons behind this. Importantly, our participants highlighted a potential role for genetic counselors in the implementation of GNBS on a larger scale by developing educational resources to facilitate obtaining informed consent and return of results.
Advances in synthesis and biological activities of benzotriazole analogues: A micro review
Authors: Bollikolla Hari Babu , Boddapati S. N. Murthy , Thangamani Swetha , Mutchu Baby Ramana , Alam Mohammed Mujahid , Hussien Mohamed , Jonnalagadda Sreekantha Babu 
Published: October 2022

AbstractAlthough the first synthesis of benzotriazole was performed in the 19th century still new methods for their preparation have developed. In this micro review authors focus mostly on the various synthetic strategies developed so far to synthesize benzotriazole and its derivatives by different strategies, such as metal‐free, metal‐assisted [3 + 2] cycloaddition reactions, cyclocondensations, flow methods, heterocyclizations, and so forth. This micro review combines recent (2005–2022 till date) information on the strategies used for the synthesis of benzotriazoles. Moreover, a brief overview of the bio applications of the benzotriazole scaffold along with pharmacological activity is also discussed.