bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study protocol of KeyPemls‐004: A phase 2 study of pembrolizumab in combination with plinabulin and docetaxel in previously treated patients with metastatic non‐small cell lung cancer and progressive disease (PD) after immunotherapy (PD‐1/PD‐L1 inhibitor) alone or in combination with platinum‐doublet chemotherapy
Authors: Liu Jia , Chen Minjiang , Gao Xiaoxing , Liu Xiaoyan , Zhao Jing , Pan Ruili , Zhong Wei , Xu Yan , Wang Mengzhao 
Published: February 2023

AbstractIntroductionImmune checkpoint inhibitor (ICI)‐based treatment regimens have become the standard of care for first‐line treatment of metastatic epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) wild‐type non‐small cell lung cancer (NSCLC). Nevertheless, most patients inevitably develop disease progression, and the mechanisms of resistance to first‐line immunotherapy are not clear. ICIs in combination with agents targeting other pathways may serve as second‐line therapy options. Plinabulin is a selective immunomodulating microtubule‐binding agent which inhibits the polymerization of tubulin monomers, with multiple mechanisms to inhibit tumor growth. Clinical studies have demonstrated preliminary the antitumor efficacy of this agent. Therefore, we hypothesize that a combination of plinabulin with programmed death 1 (PD‐1) inhibitor and docetaxel may result in higher efficacy and fewer side effects leading to better tolerance.MethodsIn this investigator‐initiated, single‐arm, open‐label, phase II trial, metastatic NSCLC patients who acquired resistance to first‐line immunotherapy‐based therapy will be enrolled. Participants will receive pembrolizumab 200 mg D1, plinabulin 30 mg/m2 D1 and D8, and docetaxel 75 mg/m2 D1 intravenously for a 21‐day cycle. The study intervention will be given until disease progression, intolerable toxicity, informed consent withdrawal or investigator decision. The primary endpoint is investigator‐based objective response rate per Response Evaluation Criteria in Solid Tumors, version 1.1. The secondary endpoints are progression‐free survival, overall survival, duration of response, and safety.DiscussionThis trial will provide evidence of the benefit and safety of pembrolizumab in combination with plinabulin and docetaxel in metastatic NSCLC patients who have been exposed and developed resistance to first‐line PD‐1/PD‐L1 inhibitor either as monotherapy or in combination with chemotherapy.
Irritant potential of different washing procedures used for heavy‐duty soiling: Short and intense or longer and mild?
Authors: Gina Michal , Wichert Katharina , Pieper Birgit , Behrens Thomas , Brüning Thomas , Fartasch Manigé 
Published: February 2023

AbstractBackgroundTo prevent irritant contact eczema even in occupational fields with heavy‐duty soiling, it is generally recommended to use ‘mild’ hand cleansers (mild detergent without grits, MC). On the other hand, since grit‐containing cleansers (GC) show a higher washing power that minimizes washing time, their usage is generally preferred in specific occupational fields.ObjectivesTo compare whether a shorter, intense washing period might cause less skin damage than a longer washing period with an MC.MethodsDifferences in cleaning time were first verified in a pilot study using standardized model dirt. In the main study, the forearms of 35 healthy volunteers were washed with three standardized procedures over a period of 3 days, either using 2 min of MC with/without hand brush or 1‐min GC. Clinical scoring, transepidermal water loss (TEWL), corneometry, colourimetry and scaliness/roughness (Visioscan) were used to evaluate the epidermal barrier, topography and irritation.ResultsThe pre‐study showed that washing time doubled when using MC vs. GC. Using GC resulted in stronger barrier disruption, even after a shorter washing period – median ΔT4–T1 TEWL 0.96 g/m2/h vs. 4.91 g/m2/h respectively, p < 0.0001. The most harmful procedure for the skin was the additional application of a hand brush (18.86 g/m2/h).ConclusionsShort‐time washing with GC damages the skin barrier more significantly in comparison to a longer application of an MC. When washing with MC, the strongest irritant reaction occurred when accompanied with hand brushing.
Applying skin protective cream and the wearing of gloves?—A randomized controlled experimental study
Authors: Gina Michal , Wichert Katharina , Kutz Gerald , Brüning Thomas , Fartasch Manigé 
Published: February 2023

AbstractBackgroundGlove occlusion might enhance skin sensitivity to a subsequent detergent challenge (occlusion effect). Thus, some skin protection creams (PC) claim to protect against this effect of occlusion, and are recommended to be used before wearing liquid‐proof gloves.ObjectivesTo evaluate the effect of PC applied prior to glove occlusion on the ‘occlusion effect’—refers to increased susceptibility of the skin to a model detergent.MethodsOne hundred and eleven volunteers were enrolled in a single‐blind, randomized study. Seven PCs were applied before glove occlusion over 7 days (D1–D7). After sodium lauryl sulphate (SLS) challenge, we compared the irritation between the areas treated with PC and occlusion alone. Clinical scoring and bioengineering methods (capacitance, transepidermal water loss [TEWL], and colourimetry [erythema]) were used to quantify the irritant reactions.ResultsAfter 1 week of occlusion and PC application, we did not observe significant changes in TEWL, nor in erythema, whereas skin hydration raised in three cream‐treated areas. On day 10, after a challenge with SLS, some products significantly aggravated the skin irritation as compared to occlusion alone.ConclusionsThe ‘occlusion effect’—shown as higher skin susceptibility to a model detergent—was not mitigated by PCs when applied prior to glove occlusion. On the contrary, some PCs might have negative effects on skin barrier function and augment such sensitivity.
Surgical techniques for mesenteric lengthening in ileoanal pouch surgery: a systematic review
Authors: Zwakman Marije , Hentzen Judith E. K. R. , Jonker Jara E. , Krikke Christina , Lange Johan F. M. , Hofker Sijbrand H. S. 
Published: February 2023

AbstractAimThe key to successful construction of an ileal pouch–anal anastomosis (IPAA) following proctocolectomy in patients with ulcerative colitis or familial adenomatous polyposis is the ability of the pouch reservoir to reach the anus well vascularized and without tension. The aim of this systematic review was to provide an overview of previously described different surgical lengthening techniques to achieve adequate length for a tension‐free IPAA.MethodPubmed, Embase and Cochrane Library databases were systematically searched. Two reviewers conducted a systematic search with combinations of keywords for the surgical procedure and surgical lengthening techniques. All publications that reported one or more surgical lengthening techniques during IPAA surgery in adult patients were selected, consisting of reviews, cohort studies, case reports, human cadaver studies and expert opinions. The primary outcomes measured were the different surgical lengthening techniques and the step‐by‐step approach they involve that can be used during surgery to achieve adequate length for an IPAA.ResultsOf 1577 records reviewed, 19 articles were included in this systematic review describing at least 1181 patients (i.e. one review, four retrospective studies, five human cadaver studies, two case reports and seven expert opinions). A total of six different surgical lengthening techniques with various subtechniques were found and described, consisting of pouch folding, construction of different types of pouches, stepladder incisions, skeletonization of vessels, division and ligation of mesenteric vessels and using an interposition vein graft. No prospective or randomized controlled trials were performed regarding this topic. Quality assessment showed a medium quality of the included studies.ConclusionDifferent surgical lengthening techniques are described in a step‐by‐step approach to create adequate mesenteric length during IPAA surgery, in patients in whom the ileal pouch cannot reach the dentate line.
Is early bowel resection better than medical therapy for ileocolonic Crohn's disease? A systematic review and meta‐analysis
Authors: Husnoo Nilofer , Gana Tabitha , Hague Adam Gary , Khan Zarnigar , Morgan Jenna L. , Wyld Lynda , Brown Steven R. 
Published: February 2023

AbstractAimThere is emerging evidence supporting early bowel resection (EBR) for ileocaecal Crohn's disease (CD) as an alternative to conventional escalation of medical therapy (MT). Here, we present a systematic review and meta‐analysis of studies comparing the outcomes of EBR with those of MT in ileocolonic CD, with a focus on ileocaecal disease.MethodologyThe MEDLINE, Embase, CINAHL and Cochrane Central Register of Controlled Trials databases were searched for studies reporting the outcomes of EBR versus MT for ileocolonic CD. The Cochrane tools for assessment of risk of bias were used to assess the methodological quality of studies.ResultsNine records (from 8 studies, with a total of 1867 patients) were included in the analysis. Six studies were observational and two were randomised controlled trials. There was a reduced need for drug therapy in the EBR arm. The rate of intestinal resection at 5 years was 7.8% in the EBR arm and 25.4% in the MT group with a pooled OR of 0.32 (95% CI 0.19, 0.54; p < 0.0001). The EBR group had a longer resection‐free survival (HR 0.56, 95% CI 0.38, 0.83; p = 0.004). These outcomes were consistent in a subgroup analysis of patients with ileocaecal disease. Morbidity and quality of life scores were similar across the two groups.ConclusionEBR is associated with a more stable remission compared to initial MT for ileocolonic Crohn's disease. There is enough evidence to support EBR as an alternative to escalation of MT in selected patients with limited ileocaecal disease.
Cognitive behavioral therapies for individuals with cerebral palsy: A scoping review
Authors: Silberg Tamar , Kapil Nisha , Caven Isabelle , Levac Danielle , Fehlings Darcy 
Published: February 2023

AbstractAimTo synthesize the evidence about the main intervention characteristics of cognitive behavioral therapies (CBTs) for individuals with cerebral palsy and identify barriers and facilitators to their success, focusing on aspects of feasibility and markers of success.MethodA scoping review methodology informed a literature search for papers published between 1991 and 2021. Articles were screened, reviewed, and categorized using the DistillerSR systematic review software, and critically appraised for quantitative and/or qualitative criteria.ResultsOut of 1265 publications identified, 14 met the inclusion criteria. Elements associated with the specific study participant characteristics (46% female; aged 6–65 years), type of CBT techniques used (third‐wave [n = 6], cognitive [n = 3], cognitive and behavioral [n = 2], biofeedback training [n = 2]), and features of the study context and methodological quality (two randomized clinical trials and small sample sizes [n ≤ 12]), were identified. Most studies had psychological targets of intervention (n = 10) and secondary physiological (n = 3) or social (n = 2) objectives. Feasibility indicators were described in nearly one‐third of the papers.InterpretationThis study highlights the high flexibility within CBT interventions, enabling their adaptation for individuals with cerebral palsy. However, relatively little, and only low‐certainty evidence was identified. More high‐quality research in terms of specific CBT techniques, optimal treatment doses, and detailed population characteristics are needed.
Preventing and protesting workplace sexual harassment: Women agro‐processing workers in Bangladesh
Authors: Sultan Maheen 
Published: February 2023

SummaryMotivationSexual harassment of women in the workplace is considered to be one of the reasons holding back women from entering work and a major reason for women dropping out of work in Bangladesh. However, paid work is an important pathway to empowerment. To enable and sustain women's entry into the formal sectors of the economy, it is important to understand their voice and agency in preventing workplace sexual harassment and from the obstacles they face in doing so.PurposeThe article explores how language and social and gender norms constrain young women's voice and agency in response to sexual harassment. Our research asked how language, gender norms, and informality in work arrangements influence young women's voice and agency in response to sexual harassment at work.Methods and approachBased on case studies with factory workers in agro‐processing firms in the outskirts of the capital, Dhaka, 21 in‐depth interviews were carried out, supplemented by participatory techniques of gender safety audits and body mapping.FindingsI show the informal nature of formal workspaces and the failure of formal institutions which create precarity for the women working there. Young women's experiences, perceptions, and articulation of sexual harassment and attempts at prevention or redress are determined by gender norms and how these norms influence the factory workspace and interactions with others in that space. I argue that sexual harassment is normalized, formal complaints mechanisms do not work, and so informal means aligned with social norms may be the only option available.Policy implicationsThe policy implications of the research include the need to recognize the informal mechanisms being used and the importance of developing a common language that will allow the “victims” to speak openly about their experiences and make complaints, increasing access to and confidence in formal complaints mechanisms and developing young women's civic and political capacities to protest harassment and seek redress.
Can We Bridge The Divide? Right‐Wing Memes as Political Education
Authors: Keehn Gabriel 
Published: February 2023

AbstractMany on the contemporary Left assume that the Right has irrevocably taken control of cyberspace. Many believe that the terrain of online memetic discourse, from 4chan to Russian interference in the 2016 election via social media, is now the domain of trolls, fascists, and neo‐Nazis. In this article, Gabriel Keehn argues against that assumption, tracing the ways in which the Right won the meme war and arguing for the educative and liberatory potential of a left counteroffensive in this still contested space.
Erythrocytosis, thrombocytosis, and rate of recurrent thromboembolic event—A population based cohort study
Authors: Larsson Anneli Enblom , Andréasson Björn , Holmberg Henrik , Liljeholm Maria , Själander Anders 
Published: February 2023

AbstractIntroductionThe management to reduce risk of thromboembolic complications in polycythemia vera and essential thrombocythemia are well established, but for other conditions with elevated hemoglobin, hematocrit, or platelets there are no consensus regarding treatment and follow up.AimsTo assess frequency of elevated blood values in patients with thromboembolic event, how many of these should be investigated further regarding myeloproliferative neoplasm and if the risk of recurrent event is depending on underlying condition.MethodsRetrospective cohort study of 3931 adult patients in the county of Norrbotten, Sweden, with thromboembolism during 2017 and 2018.ResultsOf the 3931 patients, 1195 had either elevated Hb, HCT, or platelets fulfilling the 2016 revised WHO criteria for PV and ET, and out of these 411 should be evaluated regarding underlying myeloproliferative neoplasms. Unexplained thrombocytosis and secondary erythrocytosis were associated with the highest rate of recurrent event as well as the most inferior restricted mean survival time.ConclusionElevated blood values are common in patients with thromboembolic event and the high risk of recurrent event and inferior restricted mean survival time in patients with unexplained thrombocytosis and secondary erythrocytosis implicates the importance of finding and managing the underlying condition.
Association between proprotein convertase subtilisin/kexin type 9 and subclinical cerebrovascular disease in the community
Authors: Kunimura Ayako , Yano Yuichiro , Hisamatsu Takashi , Torii Sayuki , Kondo Keiko , Kadota Aya , Fujiyoshi Akira , Okamura Tomonori , Watanabe Yoshiyuki , Shiino Akihiko , Nozaki Kazuhiko , Ueshima Hirotsugu , Miura Katsuyuki ,   the SESSA research group
Published: February 2023

AbstractBackground and purposeProprotein convertase subtilisin/kexin type 9 (PCSK9) is a new target for reducing low‐density lipoprotein cholesterol and incident cardiovascular disease, including stroke. However, the clinical relevance of circulating PCSK9 levels has been poorly elucidated in the general population, particularly in association with subclinical cerebrovascular disease including cerebral small vessel disease (CSVD) and intracranial artery stenosis (ICAS).MethodsIn community‐dwelling Japanese men (n = 526) aged 46–82 years without a history of cardiovascular disease, the associations of serum PCSK9 levels with the prevalence of CSVD and ICAS were assessed using magnetic resonance imaging. CSVD included lacunar infarction, deep and subcortical white matter hyperintensity, periventricular hyperintensity and cerebral microbleeds.ResultsThe median (interquartile range) age at baseline and serum PCSK9 levels were 69 (63–74) years and 240 (205–291) ng/ml, respectively. After adjusting for traditional cardiovascular risk factors including low‐density lipoprotein cholesterol, multivariable Poisson regression with robust error variance revealed a significant association between PCSK9 levels (per 1 SD) and ICAS (relative risks 1.18, 95% confidence interval 1.02–1.37). Multivariable ordinal logistic regression for ICAS, with stenosis graded as mild (<50%) or moderate–severe (≥50%), revealed a similar association (common odds ratio 1.31, 95% confidence interval 1.04–1.64). However, no significant association was observed between serum PCSK9 levels and CSVD.ConclusionsHigher circulating PCSK9 levels were independently associated with an ICAS prevalence but not with CSVD prevalence. The quantification of circulating PCSK9 levels may help to identify individuals at high risk for cerebrovascular disease in the general population.
Poetics and panic
Authors: Stromberg Peter G. 
Published: February 2023

AbstractAuthors in the pragmatic and phenomenological traditions offer several distinct but overlapping theories of meaning. Drawing on a number of these theories, I analyze the speech of a panic sufferer, as he recounts an attack of panic and as he has one, in order to contrast the enactment of meaning with its paralysis. This material offers an opportunity to deepen our understanding of the construction of self as it arises out of the interaction between a human being and their cultural environment.
Magnetic susceptibility, mineral chemistry, and geothermobarometry of granitoids from Lohit Plutonic Complex, Arunachal Trans‐Himalaya, Northeast India: Implications on emplacement and crystallization conditions of oxidized calc alkaline magmatic arc system
Authors: Meyase Diezeneino , Rino Vikoleno , Kumar Santosh , Nagi Rokozono 
Published: February 2023

AbstractThe Lohit Plutonic Complex (LPC) of Arunachal Trans‐Himalaya represents the northeast extension of Trans‐Himalayan magmatic arc system located in the north of Indus Tsangpo Suture Zone (ITSZ). Field relation, magnetic susceptibility (MS), and phase petrology on the granitoids of LPC was conducted in order to assess the granite series (magnetite, oxidized vs. ilmenite, reduced types), and physico‐chemical conditions of the LPC granitoid magmas. The studied granitoids are well‐exposed in the Dibang and Lohit valleys, and their MS values indicate a bi‐modal patterns corresponding to ilmenite (reduced) series (71%) and magnetite (oxidized) series (29%) granites. The variation of MS in the LPC granitoids is related to the alteration of ferromagnetic minerals, and later tectonic and deformational processes that acted upon them. The amphiboles from the LPC granitoids are calcic (CaB >1.5, Si = 6.30–7.06 apfu) and exhibit tschermak substitutions typical to their evolution in a calc alkaline, metaluminous (I‐type) felsic magmas. Al‐in‐hornblende rims estimate the emplacement of quartz diorite and granodiorite magmas at shallow (~5 km) and mid (~16 km) crustal depths. Geothermometric results point to a regime of magmatic crystallization (940–837°C for quartz diorite; 882–829°C for granodiorite) sufficiently above the solidus of respective melts. Biotites from LPC granitoids are primary to re‐equilibrated, and transitional between magnesio‐ and ferri‐biotites. Quartz diorite and granodiorite biotites evolved under oxidizing magmas (log ƒO2−14 to log ƒO2−13) in a temperature range of ~750–950°C, typical to their formation in a calc alkaline magma of subduction zone environment. However, the biotites from leucogranite appear to have evolved under a mildly reducing magma environment, most likely attained in a collisional setting. The obtained results suggest that the oxidized nature of calc alkaline, subduction‐related magmatic arc rocks of the LPC is largely modified and reduced by post‐magmatic, and later tectonothermal and deformational events that operated during Himalayan and Trans‐Himalayan orogenesis.
Dual blockages of a broad and potent neutralizing IgM antibody targeting GH loop of EV‐As
Authors: Zhu Wenbing , Li Jun , Wu Zhongxiang , Li Hui , Zhang Zhixiao , Zhu Xiaoyong , Sun Ming , Dong Shaozhong 
Published: February 2023

AbstractThe reported enterovirus A 71 (EVA71) vaccines and immunoglobin G (IgG) antibodies have no cross‐antiviral efficacy against other enterovirus A (EV‐A) which caused hand, foot and mouth disease (HFMD). Here we constructed an IgM antibody (20‐IgM) based on our previous discovery to address the resistance encountered by IgG‐based immunotherapy. Although binding to the same conserved neutralizing epitope within the GH loop of EV‐As VP1, the antiviral breath and potency of 20‐IgM are still higher than its parental 20‐IgG1. The 20‐IgM blocks the interaction between the EV‐As and its receptors, scavenger receptor class B, member 2 (SCARB2) and Kringle‐containing transmembrane protein 1(KREMEN1) of the host cell. The 20‐IgM also neutralizes the EV‐As at the post‐attachment stages, including postattachment neutralization, uncoating and RNA release inhibition after internalization. Mechanistically, the dual blockage effect of 20‐IgM is dependent on both a conserved site targeting and high affinity binding. Meanwhile, 20‐IgM provides cross‐antiviral efficacy in EV‐As orally infected neonatal ICR mice. Collectively, 20‐IgM and its property exhibit excellent antiviral activity with a dual‐blockage inhibitory effect at both the pre‐ and post‐attachment stages. The finding enhances our understanding of IgM‐mediated immunity and highlights the potential of IgM subtype antibodies against enterovirus infections.