bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clear cell injury associated with reduced expression of carbonic anhydrase II in eccrine glands consistently occurs in patients with acquired idiopathic generalized anhidrosis
Authors: Sano Kenji , Asahina Masato , Uehara Takeshi , Araki Nobuyuki , Yamanaka Yoshitaka , Matsumoto Kazuhiko , Okuyama Ryuhei 
Published: January 2021

AbstractAcquired idiopathic generalized anhidrosis (AIGA) is characterized by anhidrosis/hypohidrosis without other autonomic and neurological dysfunctions. It has been believed that AIGA patients usually present no significant morphological alterations in the secretory portion of eccrine glands consisting of clear, dark and myoepithelial cells. However, we have recently revealed morphological damage of eccrine glands in AIGA patients by immunohistochemistry. Moreover, inhibitory side‐effects against carbonic anhydrase II (CA II) by the antiepileptic reagent topiramate have been reported to cause heat intolerance mimicking AIGA. To determine the precise morphological changes and CA II expression in eccrine glands of AIGA patients, electron microscopic observation and immunohistochemistry were applied to skin of both anhidrotic (non‐sweating) and normohidrotic (sweating‐preserved) sites, taken from each patient clinically diagnosed with AIGA. We found consistent clear cell injury in eccrine glands in anhidrotic skin samples of AIGA patients. Electron micrographs demonstrated edematous, swollen and destructive damage in clear cells of eccrine glands from non‐sweating areas of almost all AIGA patients. Immunohistochemically, clear cells showed reduced CA II expression that was heterogeneously distributed in non‐sweating skin. Some areas showed almost complete loss of CA II expression in spite of preserved dark cells, and others showed mild or moderate loss of it. Selective destruction of clear cells resulting in heterogenous atrophy in AIGA patients may be important to elucidate its etiology.
Pralatrexate for refractory mycosis fungoides in two Japanese patients
Authors: Teraishi Mika , Oguro Tokuko , Kusume Ema , Kobashi Haruka , Sano Hozumi , Fujioka Ai , Yamamoto Mayuko , Nakajima Hideki , Sano Shigetoshi 
Published: January 2021

AbstractPralatrexate has been approved for the treatment of relapsed/refractory peripheral T cell lymphomas. Studies in the U.S. also support the clinical efficacy of pralatrexate to treat advanced‐stage cutaneous T‐cell lymphomas, but outcomes in Japanese patients have not yet been reported. We herein describe two Japanese patients with heavily‐pretreated relapsed/refractory mycosis fungoides that were successfully controlled by pralatrexate.
Overlooked Husbands: The Paradox of Unfree Marriage in the Carolingian World
Authors: Stone Rachel 
Published: January 2021

AbstractUnfree people in the Roman world could not legally marry, while they could in the Middle Ages. This paper explores the marriage of the unfree in the Carolingian empire (750–900 CE), a society with an intense moral concern about marriage. Carolingian churchmen wrote extensively about marriage, using a strongly gendered discourse focusing on how men should approach marriage and behave as husbands. However, these moral and legal texts rarely discussed unfree marriage, even though the practice was common. It is argued that this silence reflects the persistence of late antique class‐based gender models, in which masculinity was reserved for married property holders. Although legal prohibitions on unfree marriages had ended, Carolingian moralists continued to be influenced by patristic assumptions that these were not valid relationships. These assumptions, combined with Frankish social practices that largely excluded unfree men from other key male roles, such as arms‐bearing, meant that unfree husbands were not conceptualised as sufficiently ‘manly’ to have their marriages discussed. It is only from the tenth century onwards, when images of masculinity began to fragment more along lines of social status, that authors began explicitly to state that the Christian ideas of marriage applied to all, free and unfree.
Supraclavicular ultrasonographic real‐time guidance of peripherally inserted central catheters – A feasibility study
Authors: Kirkegaard Ellen , Lind Peter C. , Dolmer Henrik , Juhl‐Olsen Peter 
Published: January 2021

AbstractBackgroundMispositioning is common during insertion of peripherally inserted central catheters. Ultrasonographic visualization of anatomical structures may enable continuous guidance during insertion. The aim was to investigate the feasibility of ultrasonographic real‐time guidance of peripherally inserted central catheter placement using the supraclavicular fossa view.MethodsAn observational quality control study was performed including 20 patients. Ultrasonography was performed via the right supraclavicular fossa using a microconvex probe identifying the junction between the right internal jugular‐ and the subclavian vein forming the right brachiocephalic vein. The wire guide tip was identified at the junction allowing estimation of catheter length. The catheter stiffening wire was followed in real‐time into the right brachiocephalic vein towards the superior vena cava. Mispositions and the ability to redirect in real‐time were detected. Final catheter tip positions were evaluated by either fluoroscopy or a chest radiograph.ResultsCatheters were successfully placed in 19/20 patients. In all patients the junction and the right brachiocephalic vein was identified. Two thrombi were identified in the right brachiocephalic vein and left‐sided insertions were performed. In 16 of 17 right‐sided insertions, wire guide and catheter stiffening wire were visible. Of the 16 visual catheters, 15 could be followed into the right brachiocephalic vein. Real‐time mispositioning was identified in eight cases and optimal redirection was successful in seven. All ultrasound‐guided catheter length estimations were adequate.ConclusionsSupraclavicular ultrasonographic real‐time guidance for peripherally inserted central catheter placement was feasible and enabled successful placement together with detection and redirection of mispositioned catheters without delay.
Lycorine hydrochloride suppresses stress‐induced premature cellular senescence by stabilizing the genome of human cells
Authors: Zhang Weina , Yang Jiaqing , Chen Yu , Xue Renhao , Mao Zhiyong , Lu Wen , Jiang Ying 
Published: January 2021

AbstractLycorine, a natural compound isolated from the traditional Chinese medicinal herb Lycoris radiata, exhibits multiple pharmacological effects, such as anti‐inflammatory, antiviral, and anticancer effects. Accumulating evidence also indicates that lycorine might hold the potential to treat age‐associated Alzheimer's disease. However, whether lycorine is involved in delaying the onset of cellular senescence and its underlying mechanisms has not been determined. Here, we demonstrate that the salt of lycorine, lycorine hydrochloride, significantly suppressed stress‐induced premature cellular senescence (SIPS) by ~2‐fold, as determined by senescence‐associated beta‐galactosidase (SA‐β‐gal) staining and the expression of p16 and p21. In addition, pretreating cells with lycorine hydrochloride significantly inhibited the expression of CXCL1 and IL1α, two factors of the senescence‐associated secreted phenotype (SASP) in SIPS cells. Further experiments revealed that lycorine hydrochloride promoted both the homologous recombination (HR) and nonhomologous end joining (NHEJ) pathways of DNA double‐strand break (DSB) repair. Mechanistic studies suggested that lycorine hydrochloride treatment promoted the transcription of SIRT1 and SIRT6, critical longevity genes positively regulating both HR and NHEJ repair pathways, thereby stimulating DSB repair and stabilizing genomes. Inhibiting SIRT1 enzymatic activity abrogated the protective effect of lycorine hydrochloride on delaying the onset of SIPS, repairing DSBs, and restoring genome integrity. In summary, our work indicates that lycorine hydrochloride might hold therapeutic potential for treating age‐associated diseases or promoting healthy aging by stabilizing genomes.
Antibiotic prophylaxis for urinary catheter manipulation following arthroplasty: a systematic review
Authors: Roberts Tobias , Smith Toby O. , Simon Henry , Goodmaker Charles , Hing Caroline B. 
Published: January 2021

AbstractBackgroundUrinary catheter use in the peri‐ and post‐operative phase following arthroplasty may be associated with urinary tract infection (UTI) and deep prosthetic joint infection (PJI). These can be catastrophic complications in joint arthroplasty. We performed a systematic review of the evidence on use of antibiotics for urinary catheter insertion and removal following arthroplasty.MethodsElectronic databases were searched using the Healthcare Databases Advanced Search interface. Grey literature was searched. From 219 citations, six studies were deemed eligible for review. Due to study heterogeneity, a narrative approach was adopted. Methodological quality of each study was assessed using the Critical Appraisal Skills Programme appraisal tool.ResultsA total of 4696 hip and knee arthroplasties were performed on 4578 participants across all studies. Of these, 1475 (31%) were on men and 3189 (68%) on women. The mean age of study participants was 69 years. Three thousand four hundred and eighty‐nine cases (74.3%) were related to hip arthroplasty and 629 (13.4%) to knee arthroplasty. Five hundred and seventy‐eight (12.3%) were either hip or knee arthroplasty. Forty‐five PJIs were reported across all studies (0.96%). Two studies found either no PJI or no statistical difference in the rate of PJI when no antibiotic prophylaxis was used for catheter manipulation. Another study found no statistical difference in PJI rates between patients with or without preoperative bacteriuria. Where studies report potential haematogenous spread from UTIs, this association can only be assumed. Increased duration of urinary catheterization is positively associated with UTI.ConclusionIt remains difficult to justify the use of prophylactic antibiotics for catheter manipulation in well patients. Their use is not recommended for this indication.
Endometrial sampling before or after saline contrast sonohysterography in women with postmenopausal bleeding (ESPRESSO trial): A multicenter randomized controlled trial
Authors: Vroom Albertine J. , Aerts Luca , Bongers Marlies Y. , Lim Arianne C. , Pielkenrood Bart J. , Geomini Peggy M. A. J. , van Hanegem Nehalennia 
Published: January 2021

AbstractIntroductionThe aim of this study is to evaluate the quality of the endometrial sample obtained by office endometrial aspiration when performed before or after saline contrast sonohysterography (SCSH) in women with postmenopausal bleeding and a thickened endometrium. To conduct a complete, minimally invasive and cost‐effective diagnostic workup in women with postmenopausal bleeding and a thickened endometrium, ideally both the office endometrial sampling and SCSH are performed. However, it is not known whether both tests affect each other when performed one after another.Material and methodsWomen with postmenopausal bleeding and an endometrial thickness >4 mm were eligible. Women were randomized into two groups: one group received endometrial aspiration before SCSH, the other group received SCSH before endometrial aspiration. The primary outcome was the proportion of sufficient endometrial samples. Reliability of the SCSH images and pain during procedures were secondary outcomes.ResultsDuring the inclusion period, 513 eligible women with postmenopausal bleeding visited the participating hospitals, 293 of whom received information about the study. Of these women, 232 (79%) agreed to participate. In the SCSH‐aspiration group, 65 women (59%) had a sufficient endometrial sample compared with 70 (67%) in the aspiration‐SCSH group (odds ratio 1.46, 95% CI 0.83‐2.54, P = .19). The proportion of reliable sonographic images was significantly higher in the SCSH‐aspiration group (n = 88, 87%) compared with the aspiration‐SCSH group (n = 71, 74%) (OR 2.38, 95% CI 1.38‐4.99, P = .02) in the per protocol analysis.ConclusionsThis study shows that the quality of an endometrial sample in women with postmenopausal bleeding is not affected by SCSH. Both procedures can be performed in one outpatient visit to perform an optimal diagnostic workup.
Proximal lacrimal obstructions: a review
Authors: Fiorino Maria Grazia , Quaranta‐Leoni Claudia , Quaranta‐Leoni Francesco M. 
Published: January 2021

AbstractPurposeThe aims of the review are to summarize the aethiopathogenesis, management and outcomes of different treatments of proximal lacrimal obstructions.MethodsAn electronic database (PubMed, MEDLINE and Google Scholar) search of all articles written in English and non‐English language with abstract translated to English on proximal lacrimal obstructions was performed. The articles were reviewed along with their relevant cross references. Data reviewed included demographics, presentations, investigations, management, complications and outcomes.ResultsPunctoplasty is as effective as punctal dilatation with monocanalicular or bicanalicular stent in case of punctal stenosis. Dacryocystorhinostomy with retrograde intubation is more effective in case of proximal canalicular obstructions than in case of mid‐canalicular obstructions. Trephination and intubation is effective in both mid and distal canalicular obstructions in patients with no associated nasolacrimal duct obstruction. Canaliculodacryocystorhinostomy has a specific indication in case of proximal common canalicular obstruction. Bypass surgery is the preferred treatment if there is no residual patency, however surgical success may not match patient satisfaction.ConclusionOptimal choice of surgical method depends on identification of the site of obstruction. Mini‐invasive techniques should be avoided in cases that would only benefit from standard surgical treatment.
Immunotyping in tubo‐ovarian high‐grade serous carcinoma by PD‐L1 and CD8+ T‐lymphocytes predicts disease‐free survival
Authors: Bansal Akriti , Srinivasan Radhika , Rohilla Manish , Rai Bhavana , Rajwanshi Arvind , Suri Vanita , Chandra Saha Subhas 
Published: January 2021

AbstractPD‐L1 immune checkpoint inhibitor expression was evaluated in high‐grade serous carcinoma (HGSC) ovary in the context of the overall immune landscape to determine its prognostic value. Consecutive cases of HGSC, 50 who underwent upfront surgery followed by adjuvant chemotherapy (HGSC‐U) and 50 who underwent neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (HGSC‐PC) were selected. In HGSC‐PC cases, the pre‐NACT ascitic fluid cell blocks were included. Tumor‐infiltrating lymphocytes (TILs) were scored, hotspots chosen for tissue microarray construction and immunohistochemistry performed and scored for CD4 and CD8 lymphocyte subsets, CD68+ tumor‐associated macrophages (TAMs), PD‐1 and PD‐L1 expression. HGSC‐post‐chemotherapy showed increased TILs, predominantly CD8+T‐lymphocytes, compared to HGSC‐U. HGSC showed PD‐L1 expression on tumor cells and/or TAMs in 60% cases with a linear correlation to CD4+, CD8+ TIL levels. Concordant PD‐L1 expression was seen in matched pre‐ and post‐NACT tumor cells. HGSC‐PC showed higher expression of PD‐L1. There was no association of PD‐L1 cumulative proportion score or tumor cell score with outcome. Taking a cutoff for PD‐L1 CPS at 10%, immunotype I (PD‐L1+/CD‐8+), corresponding to tumors with adaptive immune evasion, showed worst disease‐free survival compared to all other immunotypes (p = 0.03) and was more significant (p = 0.01) when compared to immunotype III (PD‐L1+/CD8−). Immunotyping based on PD‐L1/CD8+ expression correlates to prognosis and outcome.
Prognostic role of TSPAN1, KIAA1324 and ESRP1 in prostate cancer
Authors: Stinnesbeck Melissa , Kristiansen Anna , Ellinger Jörg , Hauser Stefan , Egevad Lars , Tolkach Yuri , Kristiansen Glen 
Published: January 2021

AbstractThe aim of this study was to validate prostate cancer‐associated genes on transcript level and to assess the prognostic value of the most promising markers by immunohistochemistry. Based on differentially expressed genes found in a previous study, 84 genes were further validated using mRNA expression data and follow‐up information from the Cancer Genome Atlas (TCGA) prostate cancer cohort (n = 497). Immunohistochemistry was used for validation of three genes in an independent, clinically annotated prostatectomy patient cohort (n = 175) with biochemical relapse as endpoint. Also, associations with clinicopathological variables were evaluated. Eleven protein‐coding genes from the list of 84 genes were associated with biochemical recurrence‐free survival on mRNA expression level in multivariate Cox‐analyses. Three of these genes (TSPAN1, ESRP1 and KIAA1324) were immunohistochemically validated using an independent cohort of prostatectomy patients. Both ESRP1 and KIAA1324 were independently associated with biochemical recurrence‐free survival. TSPAN1 was univariately prognostic but failed significance on multivariate analysis, probably due to its strong correlation with high Gleason scores. Multistep filtering using the publicly available TCGA cohort, data of an earlier expression profiling study which profiled 3023 cancer‐associated transcripts in 42 primary prostate cancer cases, identified two novel candidate prognostic markers (ESRP1 and KIAA1324) of primary prostate cancer for further study.
The role and mechanism of the annexin A1 peptide Ac2‐26 in rats with cardiopulmonary bypass lung injury
Authors: Xu Jiyang , Yu Chengkun , Luo Junli , Guo Yuhan , Cheng Chi , Zhang Hong 
Published: January 2021

AbstractThe main causes of lung injury after cardiopulmonary bypass (CPB) are systemic inflammatory response syndrome (SIRS) and pulmonary ischaemia‐reperfusion injury (IR‐I). SIRS and IR‐I are often initiated by a systemic inflammatory response. The present study investigated whether the annexin A1 (ANX‐A1) peptidomimetic Ac2‐26 by binding to formyl peptide receptors (FPRs) inhibit inflammatory cytokines and reduce lung injury after CPB. Male rats were randomized to the following five groups (n = 6, each): sham, exposed to pulmonary ischaemic‐reperfusion (IR‐I), IR‐I plus Ac2‐26, IR‐I plus the FPR antagonist, BoC2 (N‐tert‐butyloxycarbonyl‐Phe‐Leu‐Phe‐Leu‐Phe) and IR‐I plus Ac2‐26 and BoC2. Treatment with Ac2‐26 improved the oxygenation index, an effect blocked by BoC2. Histopathological analysis of the lung tissue revealed that the degree of lung injury was significantly less (P < 0.05) in the Ac2‐26‐treated rats compared to the other experimental groups exposed to IR‐I. Ac2‐26 treatment reduced the levels of the inflammatory cytokines TNF‐α, IL‐1β, ICAM‐1 and NF‐κB‐p65 (P < 0.05) compared to the vehicle‐treated group exposed to IR‐I. In conclusion, the annexin A1 (ANX‐A1) peptidomimetic Ac2‐26 by binding to formyl peptide receptors inhibit inflammatory cytokines and reduce ischaemic‐reperfusion lung injury after cardiopulmonary bypass.
The effect of class size on grades and course evaluations: Evidence from multisection courses
Authors: Karas Alexei 
Published: January 2021

AbstractUsing rich administrative data from a small Dutch liberal arts college, I study how the number of students enrolled in a course affects student grades and course evaluations. Exploiting variation across parallel sections of the same course taught by the same instructor, I show that class size has a significant negative effect on student grades in mandatory courses, but not in electives. I show similar results for various components of student course evaluations: perceived overall course quality, perceived amount learned, student participation and engagement. I interpret these findings to be consistent with class size affecting educational outcomes through student engagement.
Detrital zircon and rutile U–Pb, Hf isotopes and heavy mineral assemblages of Israeli Miocene sands: Fingerprinting the Arabian provenance of the Levant
Authors: Morag Navot , Avigad Dov , Gerdes Axel , Abbo Avishai 
Published: January 2021

AbstractIsolated, Miocene continental basins scattered over Israel and Jordan represent the remnants of a continental‐wide fluvial system, which originated in Arabia and transported siliciclastic sediments westward to the deep Levant Basin. These basins define two geographically separated sedimentary provinces. The detrital zircon age spectra in both provinces are dominated by Neoproterozoic U‐Pb ages (550–1,000 Ma), resembling those of Paleozoic‐Mesozoic sandstones exposed along the uplifted Red Sea Rift flank. However, while the southern province exhibits two prominent peaks at ~600 and ~1,000 Ma, similar to those seen in Cambrian‐Ordovician sandstones in southern Israel and Jordan, the northern province shows an additional significant age peak at ~800 Ma and its overall spectrum resembles that of Devonian sandstones in northern Saudi Arabia. These variations distinguish the two Miocene clastic outliers as pertaining to two separate, NW‐directed transport systems delivering siliciclastic sediments from Arabia towards the deep Levant Basin. The detrital zircon U‐Pb‐Hf signal of the Israeli Miocene clastic units differs from that of the River Nile, particularly in the lack of Cenozoic‐Mesozoic‐aged zircons in the former. This allows us to distinguish the properties of the fluvial system that existed in Arabia, on the eastern side of the Red Sea, from that of the River Nile that drained its western flanks. While it is commonly accepted that the (proto‐)Nile River played a key role in the Levant Basin fill, the eastern fluvial system that prevailed on the Arabian side may have been also important.
Further delineation of the NTHL1 associated syndrome: A report from the French Oncogenetic Consortium
Authors: Boulouard Flavie , Kasper Edwige , Buisine Marie‐Pierre , Lienard Gwendoline , Vasseur Stéphanie , Manase Sandrine , Bahuau Michel , Barouk Simonet Emmanuelle , Bubien Virginie , Coulet Florence , Cusin Véronica , Dhooge Marion , Golmard Lisa , Goussot Vincent , Hamzaoui Nadim , Lacaze Elodie , Lejeune Sophie , Mauillon Jacques , Beaumont Marie‐Pascale , Pinson Stéphane , Tlemsani Camille , Toulas Christine , Rey Jean‐Marc , Uhrhammer Nancy , Bougeard Gaëlle , Frebourg Thierry , Houdayer Claude , Baert‐Desurmont Stéphanie 
Published: January 2021

AbstractBiallelic pathogenic variants in the NTHL1 (Nth like DNA glycosylase 1) gene cause a recently identified autosomal recessive hereditary cancer syndrome predisposing to adenomatous polyposis and colorectal cancer. Half of biallelic carriers also display multiple colonic or extra‐colonic primary tumors, mainly breast, endometrium, urothelium, and brain tumors. Published data designate NTHL1 as an important contributor to hereditary cancers but also underline the scarcity of available informations. Thanks to the French oncogenetic consortium (Groupe Génétique et Cancer), we collected NTHL1 variants from 7765 patients attending for hereditary colorectal cancer or polyposis (n = 3936) or other hereditary cancers (n = 3829). Here, we describe 10 patients with pathogenic biallelic NTHL1 germline variants, that is, the second largest NTHL1 series. All carriers were from the “colorectal cancer or polyposis” series. All nine biallelic carriers who underwent colonoscopy presented adenomatous polyps. For digestive cancers, average age at diagnosis was 56.2 and we reported colorectal, duodenal, caecal, and pancreatic cancers. Extra‐digestive malignancies included sarcoma, basal cell carcinoma, breast cancer, urothelial carcinoma, and melanoma. Although tumor risks remain to be precisely defined, these novel data support NTHL1 inclusion in diagnostic panel testing. Colonic surveillance should be conducted based on MUTYH recommendations while extra‐colonic surveillance has to be defined.