bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Enhancing CAR T-cell Therapy Using Fab-Based Constitutively Heterodimeric Cytokine Receptors
Authors: Righi Matteo , Gannon Isaac , Robson Matthew , Srivastava Saket , Kokalaki Evangelia , Grothier Thomas , Nannini Francesco , Allen Christopher , Bai Yuchen V. , Sillibourne James , Cordoba Shaun , Thomas Simon , Pule Martin
Published: September 2023

Abstract
Adoptive T-cell therapy aims to achieve lasting tumor clearance, requiring enhanced engraftment and survival of the immune cells. Cytokines are paramount modulators of T-cell survival and proliferation. Cytokine receptors signal via ligand-induced dimerization, and this principle has been hijacked utilizing nonnative dimerization domains. A major limitation of current technologies resides in the absence of a module that recapitulates the natural cytokine receptor heterodimeric pairing. To circumvent this, we created a new engineered cytokine receptor able to constitutively recreate receptor-heterodimer utilizing the heterodimerization domain derived from the IgG1 antibody (dFab_CCR). We found that the signal delivered by the dFab_CCR-IL2 proficiently mimicked the cytokine receptor heterodimerization, with transcriptomic signatures like those obtained by activation of the native IL2 receptor. Moreover, we found that this dimerization structure was agnostic, efficiently activating signaling through four cytokine receptor families. Using a combination of in vivo and in vitro screening approaches, we characterized a library of 18 dFab_CCRs coexpressed with a clinically relevant solid tumor–specific GD2-specific chimeric antigen receptor (CAR). Based on this characterization, we suggest that the coexpression of either the common β-chain GMCSF or the IL18 dFab_CCRs is optimal to improve CAR T-cell expansion, engraftment, and efficacy. Our results demonstrate how Fab dimerization is efficient and versatile in recapitulating a cytokine receptor heterodimerization signal. This module could be applied for the enhancement of adoptive T-cell therapies, as well as therapies based on other immune cell types. Furthermore, these results provide a choice of cytokine signal to incorporate with adoptive T-cell therapies.
Data from A Bispecific γδ T-cell Engager Targeting EGFR Activates a Potent Vγ9Vδ2 T cell–Mediated Immune Response against EGFR-Expressing Tumors
Authors: King Lisa A. , Toffoli Elisa C. , Veth Myrthe , Iglesias-Guimarais Victoria , Slot Manon C. , Amsen Derk , van de Ven Rieneke , Derks Sarah , Fransen Marieke F. , Tuynman Jurriaan B. , Riedl Thilo , Roovers Rob C. , Adang Anton E.P. , Ruben Jurjen M. , Parren Paul W.H.I. , de Gruijl Tanja D. , van der Vliet Hans J.
Published: September 2023

Abstract
Vγ9Vδ2 T cells are effector cells with proven antitumor efficacy against a broad range of cancers. This study aimed to assess the antitumor activity and safety of a bispecific antibody directing Vγ9Vδ2 T cells to EGFR-expressing tumors. An EGFR-Vδ2 bispecific T-cell engager (bsTCE) was generated, and its capacity to activate Vγ9Vδ2 T cells and trigger antitumor activity was tested in multiple in vitro, in vivo, and ex vivo models. Studies to explore safety were conducted using cross-reactive surrogate engagers in nonhuman primates (NHP). We found that Vγ9Vδ2 T cells from peripheral blood and tumor specimens of patients with EGFR+ cancers had a distinct immune checkpoint expression profile characterized by low levels of PD-1, LAG-3, and TIM-3. Vγ9Vδ2 T cells could be activated by EGFR-Vδ2 bsTCEs to mediate lysis of various EGFR+ patient–derived tumor samples, and substantial tumor growth inhibition and improved survival were observed in in vivo xenograft mouse models using peripheral blood mononuclear cells (PBMC) as effector cells. EGFR-Vδ2 bsTCEs exerted preferential activity toward EGFR+ tumor cells and induced downstream activation of CD4+ and CD8+ T cells and natural killer (NK) cells without concomitant activation of suppressive regulatory T cells observed with EGFR-CD3 bsTCEs. Administration of fully cross-reactive and half-life extended surrogate engagers to NHPs did not trigger signals in the safety parameters that were assessed. Considering the effector and immune-activating properties of Vγ9Vδ2 T cells, the preclinical efficacy data and acceptable safety profile reported here provide a solid basis for testing EGFR-Vδ2 bsTCEs in patients with EGFR+ malignancies.
Data from AXL Inhibition Improves the Antitumor Activity of Chimeric Antigen Receptor T Cells
Authors: Sakemura R. Leo , Hefazi Mehrdad , Cox Michelle J. , Siegler Elizabeth L. , Sinha Sutapa , Hansen Michael J. , Stewart Carli M. , Feigin Jennifer M. , Manriquez Roman Claudia , Schick Kendall J. , Can Ismail , Tapper Erin E. , Horvei Paulina , Adada Mohamad M. , Bezerra Evandro D. , Kankeu Fonkoua Lionel Aurelien , Ruff Michael W. , Forsman Cynthia L. , Nevala Wendy K. , Boysen Justin C. , Tschumper Renee C. , Grand Cory L. , Kuchimanchi Kameswara R. , Mouritsen Lars , Foulks Jason M. , Warner Steven L. , Call Timothy G. , Parikh Sameer A. , Ding Wei , Kay Neil E. , Kenderian Saad S.
Published: September 2023

Abstract
The receptor tyrosine kinase AXL is a member of the TYRO3, AXL, and proto-oncogene tyrosine-protein kinase MER family and plays pleiotropic roles in cancer progression. AXL is expressed in immunosuppressive cells, which contributes to decreased efficacy of immunotherapy. Therefore, we hypothesized that AXL inhibition could serve as a strategy to overcome resistance to chimeric antigen receptor T (CAR T)–cell therapy. To test this, we determined the impact of AXL inhibition on CD19-targeted CAR T (CART19)–cell functions. Our results demonstrate that T cells and CAR T cells express high levels of AXL. Specifically, higher levels of AXL on activated Th2 CAR T cells and M2-polarized macrophages were observed. AXL inhibition with small molecules or via genetic disruption in T cells demonstrated selective inhibition of Th2 CAR T cells, reduction of Th2 cytokines, reversal of CAR T-cell inhibition, and promotion of CAR T-cell effector functions. AXL inhibition is a novel strategy to enhance CAR T-cell functions through two independent, but complementary, mechanisms: targeting Th2 cells and reversing myeloid-induced CAR T-cell inhibition through selective targeting of M2-polarized macrophages.
Table S1 from HTLV-1 bZIP Factor-Induced Reprogramming of Lactate Metabolism and Epigenetic Status Promote Leukemic Cell Expansion
Authors: Toyoda Kosuke , Yasunaga Jun-ichirou , Shichijo Takafumi , Arima Yuichiro , Tsujita Kenichi , Tanaka Azusa , Salah Tarig , Zhang Wenyi , Hussein Osama , Sonoda Miyu , Watanabe Miho , Kurita Daisuke , Nakashima Kazutaka , Yamada Kyohei , Miyoshi Hiroaki , Ohshima Koichi , Matsuoka Masao
Published: September 2023

Human cluster 2 genes whose H3K27me3 in TSS's was decreased.
Figure S6 from Discovery and Characterization of ZL-2201, a Potent, Highly Selective, and Orally Bioavailable Small-molecule DNA-PK Inhibitor
Authors: Lal Shruti , Bhola Neil E. , Sun Bee-Chun , Chen Yuping , Huang Tom , Morton Vivian , Chen Kevin X. , Xia Shanghua , Zhang Haoyu , Parikh Nehal S. , Ye Qiuping , Veiby O. Petter , Bellovin David I. , Ji Yuhua
Published: September 2023

ZL-2201 reduces DNA damage-induced MCM2 phosphorylation (Ser108).
Figure S4 from Discovery and Characterization of ZL-2201, a Potent, Highly Selective, and Orally Bioavailable Small-molecule DNA-PK Inhibitor
Authors: Lal Shruti , Bhola Neil E. , Sun Bee-Chun , Chen Yuping , Huang Tom , Morton Vivian , Chen Kevin X. , Xia Shanghua , Zhang Haoyu , Parikh Nehal S. , Ye Qiuping , Veiby O. Petter , Bellovin David I. , Ji Yuhua
Published: September 2023

ZL-2201 treatment exhibits potent antitumor efficacy in vivo.
FIGURE 2 from Discovery and Characterization of ZL-2201, a Potent, Highly Selective, and Orally Bioavailable Small-molecule DNA-PK Inhibitor
Authors: Lal Shruti , Bhola Neil E. , Sun Bee-Chun , Chen Yuping , Huang Tom , Morton Vivian , Chen Kevin X. , Xia Shanghua , Zhang Haoyu , Parikh Nehal S. , Ye Qiuping , Veiby O. Petter , Bellovin David I. , Ji Yuhua
Published: September 2023

ZL-2201 inhibits DNA-PK autophosphorylation and exhibits potent antitumor efficacy in vivo. A, Unbound plasma concentration of ZL-2201 across multiple timepoints following one-time treatment with 15 and 60 mg/kg of ZL-2201 in Balb/c nude mice (n = 2–3). B, Average tumor volume of NCI-H1703 xenografts established in female Balb/c nude mice (n = 8–10/group) treated with various concentrations of ZL-2201 for a period of 21 days. QD: once a day; BID: twice a day. C, Western blot analysis of phospho-DNA-PK in NCI-H1703 mouse xenografts. Tumor tissues were harvested after every 2 hours over the course of 24 hours after the final dose. The ratio of pDNA-PK to total DNA-PK was determined in xenografts at baseline (no treatment) and after treatment with 5, 15, 30, and 60 mg/kg of ZL-2201. Individual timepoints were combined for each treatment group to show the ratio of pDNA-PK to total DNA-PK. D, Simple Western showing the pDNA-PK reduction after 15 and 60 mg/kg dose treatment in NCI-H1703 mouse xenografts collected at multiple timepoints after the final dose (n = 3).
Managemen Continuous Renal Replacement Therapy (CRRT) pada Pasien Gagal Ginjal Akut dan Syok Sepsis di ICU
Authors: Fatoni Arie Zainul , Rusly Andri , Hartono Ruddi
Published: September 2023

Angka Kejadian sepsis sekitar 6% pasien yang ada di rumah sakit. Sepsis yang tidak tertangani dengan baik akan berkembang menjadi syok septik yang akan meningkatkan mortalitas sebesar 50 – 70 %. Gagal Ginjal Akut (GGA) terjadi pada 58-87% pasien dengan syok sepsis. Pada 70% kasus GGA yang disebabkan oleh sepsis dapat memburuk dan memerlukan renal replacement therapy (RRT).            Continuous Renal Replacement Therapy (CRRT) merupakan salah satu modalitas RRT yang baik untuk pasien syok septik.

Seorang Laki-laki berusia 51 tahun, rujukan dari ICU Rumah sakit lain dengan diagnosa respiratory failure, syok sepsis, pneumonia Hospital Assosiated Pneumonia (HAP), diabetic foot dengan osteomyelitis pedis dextra, GGA Stage 3 dan Diabetes Mellitus (DM) Tipe 2. Dari klinis pasien sesak, penurunan kesadaran, disertai syok yang membutuhkan vasopressor dan dari laboratorium didapatkan ureum 277 mg/dl serta foto thorax didapatkan kesan pneumonia. Tatalaksana pada pasien ini dilakukan pemberian antibiotik, amputasi kaki kanan dan CRRT sebagai modalitas terapi GGA. CRRT dilakukan dengan mode  Continuous Venovenous Hemodialysis elama 3 hari. Pada hari ke lima klinis pasien membaik sehingga dapat pindah keluar dari ICU.

Pada kondisi syok sepsis dengan GGA, CRRT dapat menjaga stabilitas hemodinamik pasien, mengeluarkan toksin dari ginjal, menyaring sitokin dan endotoksin, mengoreksi asam-basa dan elektrolit, mengontrol volume cairan dengan tepat, memodulasi respon imun sehingga mempercepat renal recovery dan memperbaiki kondisi klinis pasien.
SEBUAH LAPORAN KASUS Sindrom Nefrotik pada Pasien Pengguna Obat Antiinflamasi Non Steroid (OAINS) pada Dewasa: sebuah Laporan Kasus
Authors: Mumtaza Hilya Itsnain , Rochmah Izzah
Published: September 2023

Pendahuluan: Obat antiinflamasi non steroid (OAINS) merupakan salah satu obat dengan efek antiinflamasi dan analgesik yang sering dikonsumi bebas oleh masyarakat umum. Namun, OAINS juga memiliki berbagai efek samping salah satunya yaitu sindrom nefrotik (SN).
Laporan Kasus: Pria usia 20 datang dengan keluhan bengkak seluruh tubuh. Bengkak muncul bertahap disertai sesak seiring meluasnya bengkak tubuh. Sesak dirasakan menetap dan tidak membaik dengan istirahat. Pasien memiliki riwayat sering mengkonsumsi obat pegal linu, tanpa resep dokter, sejak 1 tahun yang lalu. Pasien menggunakan obat tersebut kurang lebih 3-4x dalam seminggu. Pasien didiagnosa dengan sindrom nefrotik. Pada pasien dilakukan penghentian OAINS, pasien juga diberikan streoid intravena, oral ARB, serta terapi antikoagulan oral. Pasien berespon baik terhadap terapi yang diberikan ditandai dengan berkurangnya edema dan perbaikan fungsi ginjal.
Diskusi: SN adalah kumpulan gejala penyakit glomerular berupa proteinuria masif, hipoalbuminemia, edema perifer, dan/atau hiperlipidemia. Penyebab SN dibagi menjadi dua yaitu SN primer dan SN sekunder. Beberapa macam penyebab SN primer yaitu glomerulonefritis (GN) lesi minimal, nefropati membranosa, fokal segmental, atau nefropati IgA. Sedangkan GN sekunder dapat disebabkan oleh toksisitas OAINS, infeksi, gangguan metabolik, dan gangguan sistem imun.
Kesimpulan: Pada laporan kasus ini, laki-laki usia 20 tahun yang terdiagnosis SN dengan riwayat penggunaan OAINS dalam jangka waktu lama berespon baik terhadap terapi steroid. Untuk menentukan penyebab pasti serta pilihan terapi yang tepat maka diperlukan pemeriksaan seperti biopsi ginjal. Tenaga medis juga perlu melakukan anamnesis dan pemeriksaan holistik serta komprehensif terkait faktor risiko penyebab SN.
Ambulatory Blood Pressure Monitoring (ABPM): Procedure, Interpretation and Clinical Used
Authors: Samsu Nur
Published: September 2023

Mengingat peran penting hipertensi sebagai salah satu penyebab utama morbiditas dan mortalitas prematur global, maka untuk diagnosis dan tatalaksana hipertensi secara tepat, hal yang sangat penting adalah melakukan pengukuran tekanan darah (TD) yang tepat. Secara historis, diagnosis, tatalaksana, dan prediksi risiko kematian pada pasien hipertensi didasarkan pada pembacaan TD di klinik. Namun, pembacaan TD di klinik terbukti tidak selalu dapat mencerminkan TD pasien yang sebenarnya. Dilain pihak, telah banyak bukti yang menunjukkan bahwa ambulatory blood pressure monitoring (ABPM) adalah prediktor yang lebih baik untuk kejadian kardiovaskular utama dibandingkan pengukuran TD di klinik. ABPM mengurangi jumlah pembacaan yang salah, bersamaan dengan manfaat tambahan untuk memahami variabilitas dinamis TD. ABPM memungkinkan pencatatan pengukuran TD setiap 15 – 30 menit dalam 24 jam dan mengevaluasi berbagai parameter seperti TD rata-rata 24 jam, TD rata-rata siang hari, TD rata-rata malam hari, dan persentase penurunan TD pada malam hari. Tulisan ini fokus pada pentingnya ABPM, kelebihan dan keterbatasannya dibandingkan dengan pengukuran TD klinik standar serta prosedur dan interpretasinya dalam mendiagnosis dan melakukan tatalaksana hipertensi secara lebih tepat
MalnutritionProblem in Older Adults : Risk Factors,Consequences, and Therapeutic Approach
Authors: Sunarti Sri , Fatma Siti , Putri Fara , Oktavia Nur , Miamaretta Alifia , Salsabiila Syahidah
Published: September 2023

Aging is an unavoidable part of life, which means process of turning into frail person with reduce physiologic functions and increased disease susceptibility through various mechanisms, including age-related changes in lifestyle, disease conditions, sosial and environmental factors that may affect dietary behaviors and nutritional status. Malnutrition are common symptoms in elderly and are related to various factors including eating problem and comorbid diseases. Screening for eating disorder, comorbid diseases, and mental diseases such as depression, and anxiety are essential. Managing malnutrition is important, with comprehensive treatment including lifestyle changes, controlling comorbid disease, and also simple intervensions such as nutritional supplementation or modified diets could improved the health status.
Cores, corporeidades e alegrias de viver: convívios com as máscaras e mascaramentos dos teatros de tradição popular de Minas Gerais no Brasil
Authors: Braga Bya , Pereira Gabriel Couto , Marschner Jaciara Arguello
Published: September 2023

Este artigo apresenta um panorama e os resultados parciais de um projeto de pesquisa que visa apreender a atividade atual de mascarados e mascareiros nas performatividades da cultura popular mineira, a partir de revisão bibliográfica, em diálogo com o estudo da noção de bem-estar, a pesquisa em fontes orais e a realização de produção artística inspirada na pesquisa-criação. Destacam-se possíveis benefícios dos mascaramentos. Apresenta-se parte da produção artística e experiências de formação teatral em diálogo com as formas artísticas das diferentes tradições mineiras.
Teatro de animação em língua de sinais (TALS): uma nova modalidade de teatro de formas animadas
Authors: Rigo Natália Schleder , Moretti Maria de Fátima Souza
Published: September 2023

Apresentamos um recorte da pesquisa de Rigo (2020) sobre o Teatro de Animação em Língua de Sinais (TALS), artefato cultural das comunidades surdas. Uma modalidade teatral diferenciada e inovadora que compreende bonecos, máscaras, objetos, sombras e demais figuras animadas, considerando o protagonismo de artistas surdos e o uso de sua própria língua materna visual para comunicação em cena: a língua de sinais. Abordamos, neste texto, mais precisamente a Língua Brasileira de Sinais (Libras) e a formação de atores animadores surdos.
Treatment modalities of dentigerous cysts: literature review
Authors: Couto Paulo Rogério Corrêa , Moura Rafael Joshua de Lima , Freitas Thayná de Melo , Saboia Rafael de Sousa Carvalho
Published: September 2023

There are some theories regarding the emergence of dentigerous cysts. Among them, one claims they originate from the separation of the follicle in the crown of an erupted tooth, and another, that fluid accumulates between the crown and the reduced epithelium. Even with the existing research, its etiopathogenesis still remains unknown. Cysts can be treated in several ways, among them: enucleation, marsupialization, decompression, cryotherapy, endoscopy, and their combinations. Objective: To review the literature on dentigerous cyst treatment. Material and methods: This is a narrative literature review of articles written in Portuguese and English, and published from 2011 to 2021, which are available at the SciELO, BVS, and PubMed databases. Conclusion: We found that cyst enucleation is considered the treatment of choice whenever feasible, but since this technique destroys a significant amount of tissue, other more conservative options can be used. However, the adequate technique will vary according to the characteristics of the lesion and the patient.
Situating “Deformalization” within the International Court of Justice: Understanding Institutionalised Informality
Authors: Mohanty Rahul
Published: September 2023

This article approaches the International Court of Justice (ICJ) and its decisions from the lens of “deformalization”. It conceptualises “deformalization” not in a de-institutionalised sense, but as implying informality within the functioning of formal institutions. It posits that it may be useful to adopt this perspective to examine some of the actions of the ICJ, which may not be adequately explained from a purely formal standpoint. It examines various areas of deformalization within the ICJ, such as its approach towards evidence or provisional measures. It attempts to understand why and when deformalization is needed by the ICJ and concludes that the ICJ walks a tightrope between formal rules and informal application, in order to improve its effectiveness and legitimacy.
Taxonomy and nomenclature of Kalanchoe beharensis (Crassulaceae subfam. Kalanchooideae), a variable, arborescent species from Madagascar, with reference to its horticultural derivatives
Authors: SMITH GIDEON F.
Published: September 2023

The Malagasy Kalanchoe beharensis (Crassulaceae subfam. Kalanchooideae) is a variable, arborescent species from which several morphological variants have been selected for preferential distribution through the horticultural trade, with most of these generally made available under cultivar names or at least monikers presented as cultivar names. However, it is likely that some of the monikers presented as cultivar names have not been established as such under the International Code of Nomenclature for Cultivated Plants (ICNCP or Cultivated Plant Code) and serve as trade designations or even as common names only. However, trade designations are not names regulated by the ICNCP. In addition, at least some established cultivar names attributed to K. beharensis, the species, were derived from hybrid material of which K. beharensis is one parent. An overview is presented of a selection of widely used, established and apparently not established, names usually presented as cultivar names that apply to material derived from K. beharensis found in horticulture. A selection of these is illustrated. Two Groups are established under K. beharensis, K. beharensis Hairy Group and K. beharensis Glabrous Group. The nomenclature and taxonomy of K. beharensis is revisited with special reference to infraspecific designations that have not been validly published.
A remarkable new species of Commelina (Commelinaceae) from western Mexico
Authors: MALDONADO-MORENO CLAUDIA , ALVAREZ-JIMÉNEZ ABEL DE JESÚS , JUÁREZ-GUTIERREZ HÉCTOR DAVID , ALBA GUILLERMO ALATORRE-DE , MUÑIZ-CASTRO MIGUEL ÁNGEL
Published: September 2023

Commelina occulta (Commelinaceae), a new endemic species from western Mexico, is described and illustrated. The new species is related to C. tuberosa complex and morphologically close to C. standleyi but differs in having broad leaf blades, larger, axillary inflorescences, glaucous spathaceous bracts with long peduncles, besides being more robust and glabrescent. According to IUCN criteria, the species was assessed as endangered (EN). A key to the western Mexico species of Commelina is provided.
Surface-Enhanced Raman Spectroscopy (SERS) Activity of Gold Nanoparticles Prepared Using an Automated Loop Flow Reactor
Authors: Ma Haikuan , Zhang Shuwei , Yuan Guang , Liu Yan , Cao Xuan , Kong Xiangfeng , Wang Yang
Published: September 2023

This study used automatic control methods to prepare gold nanoparticles (AuNPs) as the substrate and rhodamine 6G molecule as the probe to investigate the enhancement effect, stability, and consistency of surface-enhanced Raman spectroscopy (SERS). The gold nanosols were prepared via automatic control using loop flow-reactor technology, and the synthesis of nanoparticles with different sizes was precisely controlled by optimizing the ratio of the solution required for the reaction between sodium citrate and chloroauric acid during the preparation process. The morphology, structure, and optical properties of the prepared AuNPs were investigated using field-emission scanning electron microscopy, transmission electron microscopy, and ultraviolet visible spectroscopy. Using the proposed method, AuNPs with average particle sizes of 72, 85, 93, and 103 nm were synthesized in a precisely controlled manner. The 93 nm particles exhibited good SERS activity for rhodamine 6G under 785 nm excitation with a detection limit of 2.5 × 10−10 M. The relative standard deviation of the SERS spectra synthesized multiple times was <3.5%, indicating their good sensitivity and reproducibility. The results showed that the AuNPs prepared by the automatic control of the loop-flow method have high sensitivity, stability, and reproducibility. Moreover, they exhibited notable potential for in situ measurement and quantitative analysis using SERS.
Preliminary results from the Australian Genetics of Bipolar Disorder Study: A nation-wide cohort
Authors: Lind Penelope A , Siskind Dan J , Hickie Ian B , Colodro-Conde Lucía , Cross Simone , Parker Richard , Martin Nicholas G , Medland Sarah E
Published: September 2023

Objective:

The Australian Genetics of Bipolar Disorder Study is a nation-wide cohort of adults living with bipolar disorder. The study aims to detect the relationships between genetic risk, symptom severity, and the lifetime prevalence of bipolar disorder, treatment response and medication side effects, and patterns and costs of health care usage.

Methods:

A total of 6682 participants (68.3% female; aged 44.8 ± 13.6 years [range = 18–90]) were recruited in three waves: a nation-wide media campaign, a mail-out based on prescriptions for lithium carbonate and through the Australian Genetics of Depression Study. Participants completed a self-report questionnaire. A total of 4706 (70%) participants provided a saliva sample and were genotyped and 5506 (82%) consented to record linkage of their Pharmaceutical and Medicare Benefits Schedule data.

Results:

Most participants were living with bipolar I disorder ( n = 4068) while 1622 participants were living with bipolar II disorder and 992 with sub-threshold bipolar disorder. The mean age of bipolar disorder diagnosis was 32.7 ± 11.6 years but was younger in bipolar I ( p = 2.0E-26) and females ( p = 5.7E-23). Excluding depression with onset prior to bipolar disorder diagnosis, 64.5% of participants reported one or more co-occurring psychiatric disorders: most commonly generalised anxiety disorder (43.5%) and posttraumatic stress disorder (20.7%). Adverse drug reactions were common and resulted in discontinuation rates ranging from 33.4% for lithium to 63.0% for carbamazepine.

Conclusion:

Our findings highlight the high rate of comorbidities and adverse drug reactions among adults living with bipolar disorder in the general Australian population. Future genomic analyses focus on identifying genetic variants influencing pharmacotherapy treatment response and side effects.
Victim Centered, Aggressor Focused, and Bystander Friendly: A Qualitative Analysis of Bystander Intervention Strategies and Outcomes for Sexual Harassment or Assault
Authors: Ford Kayla , Ham Lindsay S. , Nguyen Anna Marie T. , Moore Tori , Bridges Ana J. , Quetsch Lauren B.
Published: September 2023

Limited qualitative research has been conducted to understand the experiences of victims of sexual harassment or assault (SHA) when a bystander intervenes. Even less research has focused on the consequences of bystander actions from the victim’s perspective, particularly regarding the aggressor’s subsequent behavior toward the victim and occurrence of verbal or physical harm to those involved. This qualitative study aimed to address these limitations with the following research questions: (a) what strategies did victims of SHA identify bystanders use when intervening? (b) what strategies were present when the aggressor’s behavior was stopped, paused, or continued toward the victim? and (c) what strategies were present when verbal or physical harm occurred to someone involved? Adult women between the ages of 18 to 30 ( N = 25, college student = 80%) were interviewed about one situation of bystander intervention during SHA since the age of 16 years. Findings suggest that victims identified direct, distance, distract, delegate, and proximity strategies by bystanders. Most participants reported that the aggressor’s behavior stopped or paused following bystander action, and in these cases, at least one distance or direct strategy was reportedly used most frequently. Approximately, 24% and 8% of participants reported verbal or physical harm, respectively, to at least one party. Direct and distance strategies were most frequently mentioned in experiences of SHA that involved harm. When the aggressor’s behavior continued (i.e., was not altered during the event) despite bystander actions, strategies most frequently reported included distract, delegate, and proximity. Together, results suggest that bystander intervention training programs and future research may be needed to understand under what contexts certain strategies successfully prevent or thwart SHA while maintaining emotional and physical safety for those involved.
Reading(,) with and without commas
Authors: Angele Bernhard , Gutiérrez-Cordero Ismael , Perea Manuel , Marcet Ana
Published: September 2023

All major writing systems mandate the use of commas to separate clauses and list items. However, casual writers often omit mandatory commas. Little empirical or theoretical research has been done on the effect that omitting mandatory commas has on eye movement control during reading. We present an eye-tracking experiment in Spanish, a language with a clear standard as to mandatory comma use. Sentences were presented with or without mandatory commas while readers’ eye movements were recorded. There was a local increase in the go-past time for the pre-comma region when commas were presented, which was balanced out by shorter first-pass and second-pass times on the subsequent regions. In global sentence reading time, there was no evidence for an advantage of presenting commas. These findings suggest that, even when commas are mandatory, their effect is primarily to shift when processing takes place rather than to facilitate processing overall.
Management of trigeminal neuralgia: A multi-centre case study in general practice
Authors: Zakrzewska Zofia J , Hosseini-Ashrafi Parinaz , Hussain Ishrat , Moulder Zachary James , Subhash Jithu , Tan Melissa , Johnson Martin Ewart , Zakrzewska Joanna M
Published: September 2023

Background and aims

Patients often first present with symptoms of trigeminal neuralgia (TN) to primary care. However, there has been little research to determine whether the diagnosis and management of this condition is carried out according to current guidelines. Furthermore, there is little up-to-date information regarding the prevalence of TN in the UK. The aim is to estimate the prevalence of TN and to audit the diagnosis and management process of TN in primary care.

Methods

Between 2019 and 2020 a search was made at five UK GP practices with a total patient population of 55,842 using EMIS and SystmOne patient record systems to review patient consultations to identify patients coded with TN or facial pain (FP). These records were reviewed to ascertain the basis for diagnosis, management in primary care and referral to secondary care.

Results

157 patients were identified; 54 coded with FP and 103 with TN. These results indicate a prevalence of 22.3 in 10,000. There was no difference in documented symptoms between the two groups. Seven patients had all ICDH3 criteria recorded, with two meeting the requirements for TN diagnosis. 58.8% of patients with TN were started on carbamazepine, the current gold standard treatment, compared with 16.7% in the FP group. 38.2% of TN patients were referred to a range of different specialities.

Conclusion

The prevalence of TN may be higher than previously thought. Key diagnostic criteria are often omitted, leading to potential misdiagnosis or delays in diagnosis. Relatively few referrals are made, though all patients should be considered for imaging.
Seeing the Black Lives Matter Movement Through Computer Vision? An Automated Visual Analysis of News Media Images on Facebook
Authors: Kim Minchul , Bas Ozen
Published: September 2023

In this study, automated visual analysis was used to explore how the political leanings of news media are associated with their visual representation of the Black Lives Matter (BLM) movement. We analyzed more than 9,000 images posted on Facebook pages run by U.S. news media between August 2014 and October 2020 using commercially developed computer vision tools and a topic modeling algorithm. The results show that images used in BLM-related news coverage can be categorized into 10 distinctively themed groups that overlap with the main types of protest images uncovered by manual content analysis. Furthermore, news sources engaged in different visual representation practices depending on their partisan leanings. The patterns uncovered in this study imply that (de)legitimization of protests may take either active or passive forms. These findings contribute to theorization of the way news media might use social media platforms to (de)legitimize social protests, which may influence public opinion on social issues.
Single-cell analysis of human prepuce reveals dynamic changes in gene regulation and cellular communications
Authors: Tan Fei , Xuan Yuan , Long Lan , Yu Yang , Zhang Chunhua , Liang Pengchen , Wang Yaoqun , Chen Meiyu , Wen Jiling , Chen Geng
Published: September 2023

Background

The cellular and molecular dynamics of human prepuce are crucial for understanding its biological and physiological functions, as well as the prevention of related genital diseases. However, the cellular compositions and heterogeneity of human prepuce at single-cell resolution are still largely unknown. Here we systematically dissected the prepuce of children and adults based on the single-cell RNA-seq data of 90,770 qualified cells.

Results

We identified 15 prepuce cell subtypes, including fibroblast, smooth muscle cells, T/natural killer cells, macrophages, vascular endothelial cells, and dendritic cells. The proportions of these cell types varied among different individuals as well as between children and adults. Moreover, we detected cell-type-specific gene regulatory networks (GRNs), which could contribute to the unique functions of related cell types. The GRNs were also highly dynamic between the prepuce cells of children and adults. Our cell–cell communication network analysis among different cell types revealed a set of child-specific (e.g., CD96, EPO, IFN-1, and WNT signaling pathways) and adult-specific (e.g., BMP10, NEGR, ncWNT, and NPR1 signaling pathways) signaling pathways. The variations of GRNs and cellular communications could be closely associated with prepuce development in children and prepuce maintenance in adults.

Conclusions

Collectively, we systematically analyzed the cellular variations and molecular changes of the human prepuce at single-cell resolution. Our results gained insights into the heterogeneity of prepuce cells and shed light on the underlying molecular mechanisms of prepuce development and maintenance.
The link between cognitive health and neighbourhood: perceptions of the public, and of policy-makers, about problems and solutions
Authors: Stevens Madeleine , Matosevic Tihana , Suarez-Pinilla Marta , Pais Sarah , Rossor Martin , Knapp Martin
Published: September 2023

Background

Growing evidence indicates associations between neighbourhood-related factors such as pollution, social isolation and physical inactivity, and cognition, that is, our ability to think clearly, learn and remember. The evidence raises the possibility of neighbourhood intervention playing a role in protecting population cognitive health. However, there is little understanding of these associations among the public and policy-makers, what they mean and how they might be acted on. In this study we explored perceptions of the public and policy-makers about influences of neighbourhood factors on brain functioning, and how they should inform policy.

Methods

Qualitative methods were used in three phases; the study ran in parallel with a quantitative study looking at neighbourhood influences on cognition. In phase one, focus groups were conducted with middle-aged (40–69) members of the public to inform statistical modelling. In phase two, similar focus groups were held in four case study areas chosen based on the modelling results. In phase three, interviews with people in public health and policy roles were conducted, including people in the case study sites.

Results

Participants described effects on their cognition from community, culture and social interactions, access to green spaces and nature, upkeep and safety of the area, and pollution, traffic and noise. Solutions included better local consultation and involvement in policy and planning, support for community interactions and active and public transport, and education on cognition. There was little awareness, but much interest, from local policy-makers and implementers, about links between cognition and place. Barriers to implementation included lack of: effective engagement with local communities, local funding and joined-up health and neighbourhood policy.

Conclusions

People can perceive impacts of neighbourhoods on brain functioning and suggest ways local areas can be improved to support cognitive health. There is support for the idea of population-level interventions to support cognitive health.
Epidemiological and therapeutic profiles of lung cancer patients in the Hokushin Region Japan: a retrospective hospital administrative database study
Authors: Kobayashi Takashi , Nishino Yoshikazu , Takiguchi Tomoya , Kanda Shintaro , Otsuki Kengo , Tanaka Yuriko , Nakazawa Yozo , Ito Ken-ichi , Hayashi Ryuji , Yasumoto Kazuo , Uramoto Hidetaka , Hirono Yasuo , Makino Tomoe , Nakada Mitsutoshi , Yano Seiji , Koizumi Tomonobu
Published: September 2023

Objective

This study was performed to validate the epidemiology, initial treatment, and clinical practice of lung cancer patients in the Hokushin region, Japan.

Methods

We retrospectively surveyed data of 5503 newly diagnosed and registered lung cancer patients in 22 principal hospital-based cancer registries in Hokushin region linked with health insurance claims data for registered patients between 2016 and 2017.

Results

The patients consisted of 3677 (66.8%) men and 1826 (33.2%) women with a mean (range) age of 72.2 (27–103) years). Diagnoses were small cell lung cancer (n = 512, 9.4%), squamous cell carcinoma (n = 1083, 19.7%), and non-squamous non-small cell lung cancer (NSCLC; n = 3906, 70.9%). The population with stage I disease in Toyama prefecture (41.1%) was smaller than in the other three prefectures associated with reduced selection of initial surgical therapy and increased frequencies of stage IV disease (33.2%) and best supportive care (18.6%). Initial chemotherapy for stage IV non-squamous NSCLC consisted of tyrosine kinase inhibitors in 39.3% of cases for EGFR and 4% of cases for ALK-positive non-squamous NSCLC, followed by platinum compounds (25.9%) non-platinum compounds (12.9%), and immune checkpoint inhibitors (10.2%). Carboplatin was the commonly prescribed first-line cytotoxic chemotherapeutic agent (65.4% of patients under 75 years and in 96.7% of patients over 75 years).

Conclusion

This study revealed real-world data on epidemiological and treatment status in lung cancer in four prefectures in Hokushin region, Japan. Simultaneous analysis of nationwide registry and insurance data could provide valuable insights for the development of lung cancer screening and medical treatment strategies. In addition, the comparative data analysis with other lesions or countries will be useful for evaluating the differences in clinical practice of cancer managements.
The association of FGF-21 with the risk of newly diagnosed type-2 diabetes mellitus: a cross-sectional study in Southern China
Authors: You Lili , Hong Xiaosi , Wu Hongshi , Liang Diefei , Li Feng , Zheng Dinghao , Zhang Xiuwei , Liu Dan , Chen Qingyu , Yan Li , Ren Meng , Wang Wei
Published: September 2023

Background

This study investigated the relationship between fibroblast growth factor 21 (FGF-21) and newly diagnosed type-2 diabetes mellitus (T2DM).

Methods

In this cross-sectional study, FGF-21 and T2DM risk were analyzed using restricted cubic splines with univariate or multivariate logistic regression analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated via logistic regression analysis. Cluster and subgroup analyses were conducted to evaluate the associations between FGF-21 and diabetes in different subpopulations. Nomograms and ROC curves were used to explore the clinical utility of FGF-21 in the diabetes assessment model.

Results

High levels of FGF-21 were significantly associated with a high risk of T2DM after adjusting for confounding factors in both the total population and subpopulations (P for trend < 0.001). In the total population, the ORs of diabetes with increasing FGF-21 quartiles were 1.00 (reference), 1.24 (95% CI 0.56–2.80; quartile 2), 2.47 (95% CI 1.18–5.33; quartile 3), and 3.24 (95% CI 1.53–7.14; quartile 4) in Model 4 (P < 0.001), and the trend was consistent in different subpopulations. In addition, compared with the model constructed with conventional noninvasive indicators, the AUC of the model constructed by adding FGF-21 was increased from 0.668 (95% CI: 0.602–0.733) to 0.715 (95% CI: 0.654–0.777), indicating that FGF-21 could significantly improve the risk-assessment efficiency of type-2 diabetes.

Conclusion

This study demonstrated that a high level of circulating FGF-21 was positively correlated with diabetes, and levels of FGF-21 could be an important biomarker for the assessment of diabetes risk.
Malaria in adults after the start of Covid-19 pandemic: an analysis of admission trends, demographics, and outcomes in a tertiary hospital in the Gambia
Authors: Bittaye Sheikh Omar , Jagne Abubacarr , Jaiteh Lamin E. S. , Amambua-Ngwa Alfred , Sesay Abdul Karim , Ekeh Bertha , Nadjm Behzad , Ramirez Williams Estrada , Ramos Asmell , Okeahialam Basil , Effa Emmanuel , Nyan Ousman , Njie Ramou
Published: September 2023

Background

Malaria remains a major public health concern in The Gambia. The study assessed the trend of malaria admissions and outcome of adult patients admitted after the start of the COVID-19 pandemic in a tertiary hospital in The Gambia.

Methods

This was a retrospective hospital-based study and data was collected from the 18th October 2020 to 28th February 2023. Demographic data, clinical features, investigations, treatment, and outcomes were recorded.

Results

A total of 499 malaria cases were admitted to the hospital over the 29 months of the study period. Data from 320 (67.2% of the total cases) adult patients admitted into the internal medicine department were analysed. The median age was 22 years, range (15–90) and 189 (59.1%) cases were youth with a youth (15–24 years) to older adult (> 24 years) ratio of 1.4:1. The majority of the patients were male 199 (62.2) with a male to female ratio of 1.6:1. The total number of malaria cases admitted into the internal medicine department increased from 103 cases in 2021 to 182 cases in 2022and admission peaked in November in both years. The total number of admitted malaria cases during the peak of the malaria season also increased from 92 patients between September 2021 and December 2021 to 132 patients from September 2022 to December 2022.There was also an increase in both severe and uncomplicated malaria during the same period. The total mortality was 31 (9.7%) and the rate was similar in 2021 9 (8.7%) and 2022 15 (8.4%). Patients with impaired consciousness were more likely to die when compared to those without impaired consciousness [19 (23.6%) vs 12 (5%), p  ≤ 0.001]. Patients with acute kidney injury were also more likely to die when compared with those without acute kidney injury [10 (20.4%) vs 15 (7.7%), p = 0.009].

Conclusion

The findings show an emerging and consistent trend of malaria admissions and the outcome in the youth and older adult population after the start of the COVID-19 pandemic in The Gambia. This, therefore, suggests the need for the implementation of targeted malaria prevention interventions in this population to further prevent the spread of the disease to the more vulnerable population.
Chemogenetic activation of locus coeruleus neurons ameliorates the severity of multiple sclerosis
Authors: Torrillas-de la Cal Alejandro , Torres-Sanchez Sonia , Bravo Lidia , Llorca-Torralba Meritxell , Garcia-Partida Jose Antonio , Arroba Ana I. , Berrocoso Esther
Published: September 2023

Background

Most current disease-modifying therapies approved for multiple sclerosis (MS) are immunomodulatory drugs that counteract the aberrant activity of the immune system. Hence, new pharmacological interventions that drive anti-inflammatory activity and neuroprotection would represent interesting alternative therapeutic approaches or complementary strategies to treat progressive forms of MS. There is evidence of reduced noradrenaline levels and alterations to locus coeruleus (LC) noradrenergic neurons in MS patients, as well as in animal models of this disease, potentially factors contributing to the pathophysiology. Drugs that enhance noradrenaline appear to have some beneficial effects in MS, suggesting their potential to dampen the underlying pathology and disease progression.

Methods

Therefore, we explored the consequences of chronic LC noradrenergic neurons activation by chemogenetics in experimental autoimmune encephalomyelitis (EAE) mice, the most widely used experimental model of MS. LC activation from the onset or the peak of motor symptoms was explored as two different therapeutic approaches, assessing the motor and non-motor behavioral changes as EAE progresses, and studying demyelination, inflammation and glial activation in the spinal cord and cerebral cortex during the chronic phase of EAE.

Results

LC activation from the onset of motor symptoms markedly alleviated the motor deficits in EAE mice, as well as their anxiety-like behavior and sickness, in conjunction with reduced demyelination and perivascular infiltration in the spinal cord and glial activation in the spinal cord and prefrontal cortex (PFC). When animals exhibited severe paralysis, LC activation produced a modest alleviation of EAE motor symptoms and it enhanced animal well-being, in association with an improvement of the EAE pathology at the spinal cord and PFC level. Interestingly, the reduced dopamine beta-hydroxylase expression associated with EAE in the spinal cord and PFC was reversed through chemogenetic LC activation.

Conclusion

Therefore, clear anti-inflammatory and neuroprotective effects were produced by the selective activation of LC noradrenergic neurons in EAE mice, having greater benefits when LC activation commenced earlier. Overall, these data suggest noradrenergic LC neurons may be targets to potentially alleviate some of the motor and non-motor symptoms in MS.
Open-source workflow design and management software to interrogate duckweed growth conditions and stress responses
Authors: Scott Madeline , de Lange Orlando , Quaranto Xavaar , Cardiff Ryan , Klavins Eric
Published: September 2023

Duckweeds, a family of floating aquatic plants, are ideal model plants for laboratory experiments because they are small, easy to cultivate, and reproduce quickly. Duckweed cultivation, for the purposes of scientific research, requires that lineages are maintained as continuous populations of asexually propagating fronds, so research teams need to develop optimized cultivation conditions and coordinate maintenance tasks for duckweed stocks. Additionally, computational image analysis is proving to be a powerful duckweed research tool, but researchers lack software tools to assist with data collection and storage in a way that can feed into scripted data analysis. We set out to support these processes using a laboratory management software called Aquarium, an open-source application developed to manage laboratory inventory and plan experiments. We developed a suite of duckweed cultivation and experimentation operation types in Aquarium, which we then integrated with novel data analysis scripts. We then demonstrated the efficacy of our system with a series of image-based growth assays, and explored how our framework could be used to develop optimized cultivation protocols. We discuss the unexpected advantages and the limitations of this approach, suggesting areas for future software tool development. In its current state, our approach helps to bridge the gap between laboratory implementation and data analytical software for duckweed biologists and builds a foundation for future development of end-to-end computational tools in plant science.