bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-Cell Analysis Reveals a CD4+ T-cell Cluster That Correlates with PD-1 Blockade Efficacy
Authors: Kagamu Hiroshi , Yamasaki Satoshi , Kitano Shigehisa , Yamaguchi Ou , Mouri Atsuto , Shiono Ayako , Nishihara Fuyumi , Miura Yu , Hashimoto Kosuke , Imai Hisao , Kaira Kyoichi , Kobayashi Kunihiko , Kanai Yae , Shibata Tatsuhiro , Horimoto Katsuhisa 
Published: October 2022

AbstractCD4+ T-cell immunity helps clonal proliferation, migration, and cancer cell killing activity of CD8+ T cells and is essential in antitumor immune responses. To identify CD4+ T-cell clusters responsible for antitumor immunity, we simultaneously analyzed the naïve-effector state, Th polarization, and T-cell receptor clonotype based on single-cell RNA-sequencing data. Unsupervised clustering analysis uncovered the presence of a new CD4+ T-cell metacluster in the CD62Llow CD4+ T-cell subpopulation, which contained multicellular clonotypes associated with efficacy of programmed death-ligand 1 (PD-1) blockade therapy. The CD4+ T-cell metacluster consisted of CXCR3+CCR4−CCR6+ and CXCR3−CCR4−CCR6+ cells and was characterized by high expression of IL7 receptor and TCF7. The frequency of these cells in the peripheral blood significantly correlated with progression-free survival and overall survival of patients with lung cancer after PD-1 blockade therapy. In addition, the CD4+ metacluster in the peripheral blood correlated with CD4+ T-cell infiltration in the tumor microenvironment, whereas peripheral Th1 correlated with local CD8+ T-cell infiltration. Together, these findings suggest that CD62Llow CCR4−CCR6+ CD4+ T cells form a novel metacluster with predictive potential of the immune status and sensitivity to PD-1 blockade, which may pave the way for personalized antitumor immunotherapy strategies for patients.Significance:The identification of a new CD4+ T-cell metacluster that corresponds with immune status could guide effective tumor treatment by predicting response to immunotherapy using peripheral blood samples from patients.
Endometriosis-Associated Mesenchymal Stem Cells Support Ovarian Clear Cell Carcinoma through Iron Regulation
Authors: Atiya Huda I. , Frisbie Leonard , Goldfeld Ester , Orellana Taylor , Donnellan Nicole , Modugno Francesmary , Calderon Michael , Watkins Simon , Zhang Rugang , Elishaev Esther , Soong Thing Rinda , Vlad Anda , Coffman Lan 
Published: October 2022

Abstract

Ovarian clear cell carcinoma (OCCC) is a deadly and treatment-resistant cancer, which arises within the unique microenvironment of endometriosis. In this study, we identified a subset of endometriosis-derived mesenchymal stem cells (enMSC) characterized by loss of CD10 expression that specifically support OCCC growth. RNA sequencing identified alterations in iron export in CD10-negative enMSCs and reciprocal changes in metal transport in cocultured OCCC cells. CD10-negative enMSCs exhibited elevated expression of iron export proteins hephaestin and ferroportin and donate iron to associated OCCCs, functionally increasing the levels of labile intracellular iron. Iron is necessary for OCCC growth, and CD10-negative enMSCs prevented the growth inhibitory effects of iron chelation. In addition, enMSC-mediated increases in OCCC iron resulted in a unique sensitivity to ferroptosis. In vitro and in vivo, treatment with the ferroptosis inducer erastin resulted in significant death of cancer cells grown with CD10-negative enMSCs. Collectively, this work describes a novel mechanism of stromal-mediated tumor support via iron donation. This work also defines an important role of endometriosis-associated MSCs in supporting OCCC growth and identifies a critical therapeutic vulnerability of OCCC to ferroptosis based on stromal phenotype.

Significance:
Endometriosis-derived mesenchymal stem cells support ovarian clear cell carcinoma via iron donation necessary for cancer growth, which also confers sensitivity to ferroptosis-inducing therapy.
Dormant SOX9-Positive Cells Facilitate MYC-Driven Recurrence of Medulloblastoma
Authors: Borgenvik Anna , Holmberg Karl O. , Bolin Sara , Zhao Miao , Savov Vasil , Rosén Gabriela , Hutter Sonja , Garancher Alexandra , Rahmanto Aldwin Suryo , Bergström Tobias , Olsen Thale Kristin , Mainwaring Oliver J. , Sattanino Damiana , Verbaan Annemieke D. , Rusert Jessica M. , Sundström Anders , Bravo Mar Ballester , Dang Yonglong , Wenz Amelie S. , Richardson Stacey , Fotaki Grammatiki , Hill Rebecca M. , Dubuc Adrian M. , Kalushkova Antonia , Remke Marc , Čančer Matko , Jernberg-Wiklund Helena , Giraud Géraldine , Chen Xingqi , Taylor Michael D. , Sangfelt Olle , Clifford Steven C. , Schüller Ulrich , Wechsler-Reya Robert J. , Weishaupt Holger , Swartling Fredrik J. 
Published: October 2022

Abstract

Relapse is the leading cause of death in patients with medulloblastoma, the most common malignant pediatric brain tumor. A better understanding of the mechanisms underlying recurrence could lead to more effective therapies for targeting tumor relapses. Here, we observed that SOX9, a transcription factor and stem cell/glial fate marker, is limited to rare, quiescent cells in high-risk medulloblastoma with MYC amplification. In paired primary-recurrent patient samples, SOX9-positive cells accumulated in medulloblastoma relapses. SOX9 expression anti-correlated with MYC expression in murine and human medulloblastoma cells. However, SOX9-positive cells were plastic and could give rise to a MYC high state. To follow relapse at the single-cell level, an inducible dual Tet model of medulloblastoma was developed, in which MYC expression was redirected in vivo from treatment-sensitive bulk cells to dormant SOX9-positive cells using doxycycline treatment. SOX9 was essential for relapse initiation and depended on suppression of MYC activity to promote therapy resistance, epithelial–mesenchymal transition, and immune escape. p53 and DNA repair pathways were downregulated in recurrent tumors, whereas MGMT was upregulated. Recurrent tumor cells were found to be sensitive to treatment with an MGMT inhibitor and doxorubicin. These findings suggest that recurrence-specific targeting coupled with DNA repair inhibition comprises a potential therapeutic strategy in patients affected by medulloblastoma relapse.

Significance:
SOX9 facilitates therapy escape and recurrence in medulloblastoma via temporal inhibition of MYC/MYCN genes, revealing a strategy to specifically target SOX9-positive cells to prevent tumor relapse.
[RETRACTED] Comparative Aspects of the Codification of Labour Legislation in Ukraine and Leading European Countries
Authors: Lyubchik Oleksandr A. , Lytvynov Oleksandr M. , Kudinov Anton S. , Kryvonos Maksym V. , Revenko Olha I. 
Published: October 2022

Abstract
The urgency of the studied problem is due to the European integration of Ukraine and the presence in modern Ukrainian society of an acute need for codification of labour legislation. Ukraine has an extensive system of labour regulations that fail to correspond to one another and often lead to the violation of constitutional and human rights. This article aims to analyse the legislation of leading European countries in the field of codification of labour legislation in order to identify factors and problems of codification of labour legislation in Ukraine. Based on a comparative analysis of Ukrainian and European legislation in the field of codification of labour law, a list of recommendations will be presented aimed at improving the codification process of labour law in Ukraine. The materials of the article have practical value for everyone, who must participate in effective lawmaking in Ukraine.
On Synergy between Convective Equatorial Signals and Monsoon Intraseasonal Oscillations in the Bay of Bengal
Authors: Valentín Jaynise M. Pérez , Fernando Harindra J. S. , Bhat G. S. , Wijesekera Hemantha W. , Phadtare Jayesh , Gonzalez Edgar 
Published: October 2022

Abstract
The relationship between eastward-propagating convective equatorial signals (CES) along the equatorial Indian Ocean (EIO) and the northward-propagating monsoon intraseasonal oscillations (MISOs) in the Bay of Bengal (BOB) was studied using observational datasets acquired during the 2018 and 2019 MISO-BOB field campaigns. Convective envelopes of MISOs originating from just south of the BOB were associated with both strong and weak eastward CES (average speed ∼6.4 m s−1). Strong CES contributed to ∼20% of the precipitation budget of BOB, and they spurred northward-propagating convective signals that matched the canonical speed of MISOs (1–2 m s−1). In contrast, weak CES contributed to ∼14% of the BOB precipitation budget, and they dissipated without significant northward propagation. Eastward-propagating intraseasonal oscillations (ISOs; period 30–60 days) and convectively coupled Kelvin waves (CCKWs; period 4–15 days) accounted for most precipitation variability across the EIO during the 2019 boreal summer as compared with that of 2018. An agreement could be noted between high moisture content in the midtroposphere and the active phases of CCKWs and ISOs for two observational locations in the BOB. Basin-scale thermodynamic conditions prior to the arrival of strong or weak CES revealed warmer or cooler sea surface temperatures, respectively. Flux measurements aboard a research vessel suggest that the evolution of MISOs associated with strong CES are signified by local enhanced air–sea interactions, in particular the supply of local moisture and sensible heat, which could enhance deep convection and further moisten the upper troposphere.

Significance Statement
Eastward-propagating convective signals along the equatorial Indian Ocean and their relationship to the northward-propagating spells of rainfall that lead to moisture variability in the Bay of Bengal are studied for the 2018 and 2019 southwest monsoon seasons using observational datasets acquired during field campaigns. Strong convective equatorial signals spurred northward-propagating convection, as compared with weak signals that dissipated without significant northward propagation. Wave spectral analysis showed CCKWs (period 4–15 days), and eastward ISOs (period 30–60 days) accounted for most of the precipitation variability, with the former dominating during the 2018 boreal summer. High moisture periods observed from radiosonde measurements show agreement with the active phases of CCKWs and ISOs.
Feasibility of pair-housing of rats after cranial implant surgery
Authors: Evers Judith , Sridhar Karthik , Lowery Madeleine 
Published: October 2022

Rat models employing cranial implants are increasingly employed to facilitate neural stimulation and recording in freely moving animals. Due to possible damage to wound, implant or attached devices, rats with cranial implants are traditionally housed singly, and little information is available on group- or pair-housing. Here we describe a protocol for pair-housing rats following cranial implant surgery and describe our experience with pair-housing during post-surgical recovery and up to 16 weeks following surgery. Thirty-six adult Wistar rats of both sexes were implanted with deep brain stimulation electrodes. Ten rats were equipped with an additional wireless headstage. Rats were housed in stable pairs before surgery and re-introduced 0–18 h post-surgery. Rat grimace scores did not indicate pain after conclusion of the analgesia protocol, physiological parameters were in the normal range three days post-surgery and weight loss did not exceed 10%. Rats with a cement cap only were pair-housed continuously without damage to the headcap. Rats carrying an additional fragile headstage had to be separated during lights-off periods to prevent headstage damage but could be pair-housed during lights-on periods. Pair-housing is a feasible and effective method to facilitate the rats’ need for social companionship following cranial implant surgery.
Comparison of two Specialized Cleft Palate Feeders
Authors: Penny Cameron , Nugent Kendra-Ann , Gilgan Holly , Bezuhly Michael 
Published: October 2022

Objective To evaluate feeding efficiency and weight gain in infants with cleft palate fed using 1 of the 2 specialty feeders. Design Retrospective cohort study. Setting Cleft palate clinic in a tertiary pediatric hospital. Participants Infants with cleft palate (with or without cleft lip) fed using the Medela SpecialNeeds® Feeder (n = 39) or the Dr. Brown's® Specialty Feeding System (n = 16) and who had documented feeding and growth data available from the time of initial assessment in the first month of life and at subsequent follow-up between 2 and 4 months. Primary Outcome Measure Feeding velocity (mL/min). Secondary Outcomes Measures Calorie velocity (kcal/min), weight gain, and complications associated with poor feeding. Results No statistically significant differences in feeding or calorie velocities were identified between infants with cleft palate fed with the Medela SpecialNeeds® feeder and those fed with the Dr. Brown's® feeder. Mean weight z-scores by month did not differ significantly between the 2 bottle groups at the time of initial assessment (P = .84) and follow-up (P = .20). Mean weight z-scores by month for the infants included in this study fell below the 50th percentile. The proportion of infants who developed otitis media, reflux requiring treatment, or who required hospital admission for nasogastric (NG) feeds did not differ significantly between the 2 groups. Conclusions Despite being adequately powered for the primary outcome, no significant differences were identified between infants fed with the Medela or the Dr. Brown's feeders in terms of feeding velocity, calorie velocity, weight gain, or complications.
Porous Polyethylene Versus Autologous Costochondral Reconstruction for Microtia: Incidence and Analysis of Secondary Procedures
Authors: Varagur Kaamya , Zubovic Ema , Skolnick Gary B. , Buss Joanna , Snyder-Warwick Alison , Reinisch John , Patel Kamlesh B. 
Published: October 2022

Objective To examine the frequency of autologous and alloplastic ear reconstructions for patients with microtia in the United States, and describe post-index procedure rates associated with each method. Design Retrospective cohort study. Setting Claims data from 500 + hospitals from IBM® MarketScan® Commercial and Multi-State Medicaid databases. Patients/Participants A total of 649 patients aged 1 to 17 years with International Classification of Diseases, ninth/tenth revision (ICD-9/10) diagnoses for microtia, congenital absence of the ear, or hemifacial microsomia. Interventions Alloplastic or autologous ear reconstruction between 2006 and 2018. Main Outcome Measure Post-index procedures performed within 1 year following the index repair, analyzed across the study period and separately for each half of the study period (2006-2012, 2012-2018). Results A total of 486 (75%) qualifying patients received autologous and 163 (25%) received alloplastic reconstruction. Secondary procedure rates were significantly higher in the autologous group at 90 days ( P = .034), 180 days ( P < .001), and at 365 days ( P < .001). Alloplastic reconstruction accounted for 23.2% of reconstructions in the first half of the study period compared with 26.7% in the second half ( P = .319). One-year secondary procedure rates in the autologous group were not significantly different between both halves of the study period (69.7% vs 67.1%, P = .558), but were significantly lower in the second half for the alloplastic group (44.9% vs 20.2%, P = .001). Conclusions In these databases, autologous reconstruction is more common than alloplastic reconstruction. Autologous reconstruction is staged, with most undergoing a secondary procedure between 3 months and 1 year postoperatively. Secondary procedure rates decreased over time in patients undergoing alloplastic reconstruction.
Feasibility of a tailored and virtually supported home exercise program for people with multiple myeloma using a novel eHealth application
Authors: Purdy Graeme M. , Venner Chris P. , Tandon Puneeta , McNeely Margaret L. 
Published: October 2022

Introduction eHealth exercise interventions have the unique ability to leverage the benefits of in-person programming (tailoring and supervision) with the benefits of home programming (flexibility). There may be a role for eHealth-delivered exercise for people with multiple myeloma (MM), as exercise tailoring and supervision are critical for successful outcomes due to the significant impacts/risks of myeloma-related side effects. The purpose of this study was to determine the safety, feasibility, and preliminary efficacy of a 12-week virtually supported eHealth exercise program. Methods Participants with MM completed a 12-week virtually supported home exercise program involving virtually supervised group workouts, independent workouts, and aerobic exercise. Tailoring was facilitated by the functionality of HEAL-Me, a novel eHealth app. Participants completed virtual fitness assessments and questionnaires at baseline and week 12. Results Twenty-nine participants consented, 26 completed all follow-up testing (90%). Exercise adherence was 90% (group), 83% (independent), and 90% (aerobic). No serious adverse events (grade ≥3) occurred. Significant improvements were found for quality of life and physical fitness. There was a high level of program/app satisfaction: 96% of participants agreed or strongly agreed that the exercise program was beneficial, 93% found it enjoyable, 89% were satisfied or very satisfied with delivery through the HEAL-Me app, and 48% felt that the eHealth program helped them manage cancer-related symptoms and side-effects. Conclusion An eHealth intervention that is individually tailored and includes virtual supervision and active support from the healthcare team is feasible and acceptable to people with MM. The findings from this study warrant investigation using a large-scale randomized controlled trial.
Patterns of Head and Neck Injuries in Urban India: A Multicenter Study
Authors: Kim Eric K. , Suri Deepak , Mahajan Anshul , Bhandarkar Prashant , Khajanchi Monty , Gadgil Anita , Ranganathan Kavitha , Gerdin Warnberg Martin , Roy Nobhojit , Raykar Nakul P. 
Published: October 2022

ObjectiveThe pattern of head and neck injuries has been well studied in high‐income countries, but the data are limited in low‐ and middle‐income countries, which are disproportionately affected by trauma. We examined a prospective multicenter database to describe patterns and outcomes of head and neck injuries in urban India.Study DesignRetrospective review of trauma registry.SettingFour tertiary public hospitals in Mumbai, Delhi, Kolkata.MethodsWe identified patients with isolated head and neck injuries using International Classification of Diseases, 10th Revision (ICD‐10) codes and excluded those with traumatic brain and/or ophthalmic injuries and injuries in other body regions.ResultsOur cohort included 171 patients. Most were males (80.7%) and adults aged 18 to 55 years (60.2%). Falls (36.8%) and road traffic accidents (36.3%) were the 2 predominant mechanisms of injury. Overall, 35.7% required intensive care unit (ICU) admission, and 11.7% died. More than 20% of patients were diagnosed with “unspecified injury of neck.” Those with the diagnosis had a higher ICU admission rate (51.4% vs 31.3%, P =. 025) and mortality rate (27.0% vs 7.5%, P =. 001) than those without the diagnosis.ConclusionIsolated head and neck injuries are not highly prevalent among Indian trauma patients admitted to urban tertiary hospitals but are associated with high mortality. Over a fifth of patients were diagnosed with “unspecified injury of neck,” which is associated with more severe clinical outcomes. Exactly what this diagnosis entails and encompasses remains unclear.
LncRNA SNHG16 promotes development of oesophageal squamous cell carcinoma by interacting with EIF4A3 and modulating RhoU mRNA stability
Authors: Ren Lihua , Fang Xin , Shrestha Sachin Mulmi , Ji Qinghua , Ye Hui , Liang Yan , Liu Yang , Feng Yadong , Dong Jingwu , Shi Ruihua 
Published: October 2022

Abstract
Background
Numerous studies have revealed that long noncoding RNAs (lncRNAs) are closely related to the development of many diseases and carcinogenesis. However, their specific biological function and molecular mechanism in oesophageal squamous cell carcinoma (ESCC) remains unclear.

Methods
RNA-Seq was performed to determine the differential expressions of lncRNAs in ESCC, and the level of SNHG16 expression was detected in ESCC and intraepithelial neoplasia (IEN) samples. In vitro and in vivo experiments were performed to explore the role of SNHG16 and the interaction of EIF4A3 and Ras homologue family member U (RhoU) signalling.

Results
One hundred and seventy-five upregulated and 134 downregulated lncRNAs were identified by RNA-Seq. SNHG16 was highly expressed in ESCC and intraepithelial neoplasia (IEN) samples, and its expression level was correlated with tumour differentiation and T stage. Overexpression of SNHG16 can facilitate ESCC cell proliferation and metastasis. Mechanistically, we noticed that SNHG16 could bind RNA binding protein (RBP)-eukaryotic translation initiation factor (EIF4A3) and interact with it to form a complex. Importantly, the coalition of SNHG16 and EIF4A3 ultimately regulated Ras homologue family member U (RhoU). SNHG16 modulated RhoU expression by recruiting EIF4A3 to regulate the stability of RhoU mRNA. Knockdown of RhoU further alleviated the effect of the SNHG16 oncogene in ESCC cells.

Conclusions
The newly identified SNHG16–EIF4A3–RhoU signalling pathway directly coordinates the response in ESCC pathogenesis and suggests that SNHG16 is a promising target for potential ESCC treatment.
The utility of diffusion-weighted imaging in patients with spinal cord infarction: difference from the findings of neuromyelitis optica spectrum disorder
Authors: Kobayashi Makoto 
Published: October 2022

Abstract
Background
Magnetic resonance imaging (MRI) plays a crucial role in diagnosing spinal cord infarction (SCI). However, the findings are often indistinguishable from those of other intramedullary diseases, such as neuromyelitis optica spectrum disorder (NMOSD). Although diffusion-weighted imaging (DWI) is a promising technique, the utility for discriminating SCI from NMOSD remains unclear because the DWI findings of acute NMOSD lesions have not been investigated in detail.

Methods
Clinical and MRI findings were retrospectively evaluated in 15 and 12 patients with acute SCI and NMOSD, respectively. First, clinical characteristics were compared between the SCI and NMOSD groups. Second, MRI abnormalities were examined to find differences between these groups. Third, in the SCI group, factors influencing T2 and DWI abnormalities were analyzed using the mixed-effects logistic regression analysis.

Results
The proportion of female patients was higher in the NMOSD group (92%) than in the SCI (40%). The time from symptom onset to nadir was smaller in the SCI group (median [interquartile range]; 4 [0.1–8.3] hours) than in the NMOSD (252 [162–576]). On T2-weighted images, SCI lesions had smaller length than NMOSD (2 [1–2] and 5 [2–7] vertebral segments, respectively). Focal lesions within the T9–L2 level were found only in patients with SCI. DWI hyperintensity was observed both in the SCI (frequency, 100%) and NMOSD (60%) groups. On apparent diffusion coefficient (ADC) maps, the hyperintensities of SCI had corresponding hypointensities, whereas those of NMOSD were isointense and a large portion of NMOSD lesions had hyperintense signals. Owl’s eyes sign and pencil-like hyperintensity, typically reported as T2 findings suggestive of SCI, were also found on DWI. Posterior linear hyperintensity was frequently detected on DWI in patients with posterior spinal artery infarction. The presence of MRI abnormality revealing SCI was modeled with the time from symptom onset, imaging sequence and plane, and affected vascular territory.

Conclusions
DWI and ADC maps help distinguish SCI from NMOSD. The time from symptom onset, imaging sequence, and imaging plane should be considered when MRI findings are interpreted in patients with suspected SCI.