bluuebunny/crossref_metadata_2025_split huggingface dataset:
The aberrant levels of decorin induce damages of human salivary gland epithelial cells and polarization of macrophages
Authors: Gao Rongfen , Tang Jungen , Dong Yuanji , Ming Bingxia , Yu Zhihua , Zhong Jixin , Dong Lingli 
Published: April 2022

ABSTRACT

Objectives
This study aimed to preliminarily address the levels of decorin (DCN, a critical component of extracellular matrix) and its potential roles in primary Sjögren’s syndrome (pSS).

Methods
DCN levels were determined in the salivary glands of experimental SS (ESS) mice and pSS patients by RNA sequencing, bioinformatics analysis, or immunohistochemical staining. Its correlation with interested genes and co-localization with a putative receptor was studied in pSS patients. In addition, its potential roles on salivary gland epithelium and macrophages were tested by exogenous administration to corresponding cell lines, followed by the evaluation of apoptosis using flow cytometry or cytokine expression using quantitative real-time polymerase chain reaction.

Results
Our data revealed a significant elevation of DCN in the salivary glands of the ESS mice model and pSS patients. In addition, the bioinformatics analysis of DCN in the GSE40611 (RNA-seq, parotid glands) dataset displayed an elevation of the DCN level in the parotid glands of pSS patients that positively correlated with several chemokines (CXCL13, CXCL9, and CCL20), Interleukin -1 β (IL1 -β), and caspase3 but negatively correlated with the proliferation relative gene MKI67. The stimulatory effects of DCN on the salivary gland epithelial cells (A253 cell line) and macrophages have been determined as they are considered active participants in the progression of SS. The data showed that DCN induced the apoptosis of A253 cells and polarization of macrophages towards the M1 phenotype, characterized by the expression of pro-inflammatory cytokines.

Conclusions
Our study provided preliminary evidence to understand the clinical significance of DCN in pSS and broadened our horizons in understanding the mechanism of pSS.
A systematic comparison of FOSL1, FOSL2 and BATF-mediated transcriptional regulation during early human Th17 differentiation
Authors: Shetty Ankitha , Tripathi Subhash Kumar , Junttila Sini , Buchacher Tanja , Biradar Rahul , Bhosale Santosh D , Envall Tapio , Laiho Asta , Moulder Robert , Rasool Omid , Galande Sanjeev , Elo Laura L , Lahesmaa Riitta 
Published: April 2022

AbstractTh17 cells are essential for protection against extracellular pathogens, but their aberrant activity can cause autoimmunity. Molecular mechanisms that dictate Th17 cell-differentiation have been extensively studied using mouse models. However, species-specific differences underscore the need to validate these findings in human. Here, we characterized the human-specific roles of three AP-1 transcription factors, FOSL1, FOSL2 and BATF, during early stages of Th17 differentiation. Our results demonstrate that FOSL1 and FOSL2 co-repress Th17 fate-specification, whereas BATF promotes the Th17 lineage. Strikingly, FOSL1 was found to play different roles in human and mouse. Genome-wide binding analysis indicated that FOSL1, FOSL2 and BATF share occupancy over regulatory regions of genes involved in Th17 lineage commitment. These AP-1 factors also share their protein interacting partners, which suggests mechanisms for their functional interplay. Our study further reveals that the genomic binding sites of FOSL1, FOSL2 and BATF harbour hundreds of autoimmune disease-linked SNPs. We show that many of these SNPs alter the ability of these transcription factors to bind DNA. Our findings thus provide critical insights into AP-1-mediated regulation of human Th17-fate and associated pathologies.
The Collapse of Infectious Disease Diagnoses Commonly Due to Communicable Respiratory Pathogens During the Coronavirus Disease 2019 Pandemic: A Time Series and Hierarchical Clustering Analysis
Authors: Zhang Ali , Surette Matthew D , Schwartz Kevin L , Brooks James I , Bowdish Dawn M E , Mahdavi Roshanak , Manuel Douglas G , Talarico Robert , Daneman Nick , Shurgold Jayson , MacFadden Derek 
Published: April 2022

Abstract

Background
Nonpharmaceutical interventions such as physical distancing and mandatory masking were adopted in many jurisdictions during the coronavirus disease 2019 pandemic to decrease spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We determined the effects of these interventions on incidence of healthcare utilization for other infectious diseases.

Methods
Using a healthcare administrative dataset, we employed an interrupted time series analysis to measure changes in healthcare visits for various infectious diseases across the province of Ontario, Canada, from January 2017 to December 2020. We used a hierarchical clustering algorithm to group diagnoses that demonstrated similar patterns of change through the pandemic months.

Results
We found that visits for infectious diseases commonly caused by communicable respiratory pathogens (eg, acute bronchitis, acute sinusitis) formed distinct clusters from diagnoses that often originate from pathogens derived from the patient’s own flora (eg, urinary tract infection, cellulitis). Moreover, infectious diagnoses commonly arising from communicable respiratory pathogens (hierarchical cluster 1: highly impacted diagnoses) were significantly decreased, with a rate ratio (RR) of 0.35 (95% confidence interval [CI], .30–.40; P &lt; .001) after the introduction of public health interventions in April–December 2020, whereas infections typically arising from the patient’s own flora (hierarchical cluster 3: minimally impacted diagnoses) did not demonstrate a sustained change in incidence (RR, 0.95 [95% CI, .90–1.01]; P = .085).

Conclusions
Public health measures to curtail the incidence of SARS-CoV-2 were widely effective against other communicable respiratory infectious diseases with similar modes of transmission but had little effect on infectious diseases not strongly dependent on person-to-person transmission.
Survival Outcomes of Adjuvant Chemotherapy in Elderly Patients with Stage III Colon Cancer
Authors: Khalil Lana , Gao Xingyu , Switchenko Jeffrey M , Alese Olatunji B , Akce Mehmet , Wu Christina , Diab Maria , El-Rayes Bassel F , Shaib Walid L 
Published: April 2022

Abstract

Background
The survival impact of multi-agent (MAC) compared with single-agent (SAC) adjuvant chemotherapy (AC) in elderly patients with stage III colon cancer (CC) remains controversial. The aim of this study was to compare survival outcomes of MAC and SAC in this population utilizing the National Cancer Database (NCDB).

Patients and Methods
Patients aged ≥70 years with pathological stage III CC diagnosed in 2004-2015 were identified in the NCDB. Univariate and multivariable analyses were conducted, and Kaplan-Meier analysis and Cox proportional hazard models were used to identify associations between MAC vs. SAC and overall survival (OS).

Results
Among 41 707 elderly patients (≥70 years old) with stage III CC, about half (n = 20 257; 48.5%) received AC; the majority (n = 12 923, 63.8%) received MAC. The median age was 79 (range 70-90). The majority were female (n = 11 201, 55.3%), Caucasians (88%) and had moderately differentiated tumor grade (n = 12 619, 62.3%), tumor size &gt;4 cm (11 785, 58.2%), and negative surgical margins (18 496, 91.3%). Low-risk stage III CC constituted 50.6% (n = 10 264) of the study population. High-risk stage III CC was associated with worse OS compared with low-risk disease (HR 0.35, 0.34-0.36, P &lt; .001). Multi-agent chemotherapy was associated with a better 5-year OS compared with SAC (P &lt; .001). High-risk stage III patients who received MAC vs. SAC had an OS of 4.2 vs. 3.4 years, respectively (P &lt; .001). Low-risk stage III patients who received MAC vs. SAC had a median OS of 8.5 vs. 7 years (P &lt; .001). In univariate and multivariable analyses, male sex, positive surgical margin, insurance and facility types, age, year of diagnosis, tumor size, and Charlson-Deyo score of &gt;2 were associated with worse OS (P &lt; .05).

Conclusions
Any adjuvant chemotherapy has a trend of survival benefits. Multi-agent chemotherapy seems to have an enhanced benefit in the 70-75 age group. Multi-agent chemotherapy seemed to have similar efficacy as SAC in those aged &gt;76 years.
A kaleidoscope of photosynthetic antenna proteins and their emerging roles
Authors: Arshad Rameez , Saccon Francesco , Bag Pushan , Biswas Avratanu , Calvaruso Claudio , Bhatti Ahmad Farhan , Grebe Steffen , Mascoli Vincenzo , Mahbub Moontaha , Muzzopappa Fernando , Polyzois Alexandros , Schiphorst Christo , Sorrentino Mirella , Streckaité Simona , van Amerongen Herbert , Aro Eva-Mari , Bassi Roberto , Boekema Egbert J , Croce Roberta , Dekker Jan , van Grondelle Rienk , Jansson Stefan , Kirilovsky Diana , Kouřil Roman , Michel Sylvie , Mullineaux Conrad W , Panzarová Klára , Robert Bruno , Ruban Alexander V , van Stokkum Ivo , Wientjes Emilie , Büchel Claudia 
Published: April 2022

Abstract
Photosynthetic light-harvesting antennae are pigment-binding proteins that perform one of the most fundamental tasks on Earth, capturing light and transferring energy that enables life in our biosphere. Adaptation to different light environments led to the evolution of an astonishing diversity of light-harvesting systems. At the same time, several strategies have been developed to optimize the light energy input into photosynthetic membranes in response to fluctuating conditions. The basic feature of these prompt responses is the dynamic nature of antenna complexes, whose function readily adapts to the light available. High-resolution microscopy and spectroscopic studies on membrane dynamics demonstrate the crosstalk between antennae and other thylakoid membrane components. With the increased understanding of light-harvesting mechanisms and their regulation, efforts are focusing on the development of sustainable processes for effective conversion of sunlight into functional bio-products. The major challenge in this approach lies in the application of fundamental discoveries in light-harvesting systems for the improvement of plant or algal photosynthesis. Here, we underline some of the latest fundamental discoveries on the molecular mechanisms and regulation of light harvesting that can potentially be exploited for the optimization of photosynthesis.
Update on the Role and Utility of Extracellular Vesicles in Hematological Malignancies
Authors: Bazzoni Riccardo , Tanasi Ilaria , Turazzi Nice , Krampera Mauro 
Published: April 2022

Abstract
Extracellular vesicles (EVs) are membrane-surrounded cellular particles released by virtually any cell type, containing numerous bioactive molecules, including lipids, proteins, and nucleic acids. EVs act as a very efficient intercellular communication system by releasing their content into target cells, thus affecting their fate and influencing several biological processes. EVs are released both in physiological and pathological conditions, including several types of cancers. In hematological malignancies (HM), EVs have emerged as new critical players, contributing to tumor-to-stroma, stroma-to-tumor, and tumor-to-tumor cell communication. Therefore, EVs have been shown to play a crucial role in the pathogenesis and clinical course of several HM, contributing to tumor development, progression, and drug resistance. Furthermore, tumor EVs can reprogram the bone marrow (BM) microenvironment and turn it into a sanctuary, in which cancer cells suppress both the normal hematopoiesis and the immunological antitumor activity, conferring a therapy-resistant phenotype. Due to their physicochemical characteristics and pro-tumor properties, EVs have been suggested as new diagnostic biomarkers, therapeutic targets, and pharmacological nanocarriers. This review aims to provide an update on the pathogenetic contribution and the putative therapeutic utility of EVs in hematological diseases.
Timescales modulate optimal lysis–lysogeny decision switches and near-term phage reproduction
Authors: Shivam Shashwat , Li Guanlin , Lucia-Sanz Adriana , Weitz Joshua S 
Published: April 2022

AbstractTemperate phage can initiate lysis or lysogeny after infecting a bacterial host. The genetic switch between lysis and lysogeny is mediated by phage regulatory genes as well as host and environmental factors. Recently, a new class of decision switches was identified in phage of the SPbeta group, mediated by the extracellular release of small, phage-encoded peptides termed arbitrium. Arbitrium peptides can be taken up by bacteria prior to infection, modulating the decision switch in the event of a subsequent phage infection. Increasing the concentration of arbitrium increases the chance that a phage infection will lead to lysogeny, rather than lysis. Although prior work has centered on the molecular mechanisms of arbitrium-induced switching, here we focus on how selective pressures impact the benefits of plasticity in switching responses. In this work, we examine the possible advantages of near-term adaptation of communication-based decision switches used by the SPbeta-like group. We combine a nonlinear population model with a control-theoretic approach to evaluate the relationship between a putative phage reaction norm (i.e. the probability of lysogeny as a function of arbitrium) and the extent of phage reproduction at a near-term time horizon. We measure phage reproduction in terms of a cellular-level metric previously shown to enable comparisons of near-term phage fitness across a continuum from lysis to latency. We show the adaptive potential of communication-based lysis–lysogeny responses and find that optimal switching between lysis and lysogeny increases the near-term phage reproduction compared to fixed responses, further supporting both molecular- and model-based analyses of the putative benefits of this class of decision switches. We further find that plastic responses are robust to the inclusion of cellular-level stochasticity, variation in life history traits, and variation in resource availability. These findings provide further support to explore the long-term evolution of plastic decision systems mediated by extracellular decision-signaling molecules and the feedback between phage reaction norms and ecological context.
Technology-Enhanced CPD: Sailing Safely Through the COVID-19 Storm and Building a Better New Normal
Authors: Hlede Vjekoslav 
Published: April 2022

Abstract:
COVID-19 has shocked our CME/CPD world and the broader educational system. It has activated existing semi-dormant forces, creating a perfect storm of changes. While the crisis will hopefully be over soon, other forces are here to stay. This paper discusses (1) the interaction between the newly emboldened forces, (2) strategies we can use to navigate through the COVID storm safely, and (3) how we can utilize all available forces to create long-lasting positive change in CME/CPD.
Syphilis Presenting as Hepatitis in an HIV-Infected Patient
Authors: Ong Aaron Lemuel , Gutierrez-Macabaya Arlene 
Published: April 2022

Abstract
Syphilis presents with protean manifestations. We report the case of a 24-year-old Filipino, working in Zambia for the past 2 months, presenting with a 2-week history of fever and jaundice. Maculopapular rashes were noted on both palms of the hands and both soles of the feet. Workup revealed an abnormal cholestatic pattern of liver function tests, while negative for malaria, viral hepatitis, and bacteremia. He tested positive for both HIV and VDRL (Venereal Disease Research Laboratory). A magnetic resonance cholangiopancreatography showed only hepatomegaly and no signs of cholangiopathy or hepatobiliary tree anomalies. After administration of a single dose of penicillin G, resolution of fever and jaundice and normalization of liver enzymes were noted. Syphilitic hepatitis was the primary diagnosis because of the following: demonstration of liver injury, positive serology for syphilis, and exclusion of other causes of liver injury with resolution upon penicillin G administration.
18F-fluorodeoxyglucose PET and PET/computed tomography for the evaluation of immunoglobulin G4-related disease: a systematic review
Authors: Francesco Dondi , Domenico Albano , Pietro Bellini , Giulia Volpi , Raffaele Giubbini , Francesco Bertagna 
Published: April 2022

Background
In the last years, 18F-fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) has demonstrated its utility for the evaluation of immunoglobulin G4 (IgG4)-related disease (IgG4RD). The studies are, however, really heterogeneous and different. The aim of this review is, therefore, to analyze the diagnostic performance of 18F-FDG PET and PET/CT for the assessment of IgG4RD.

Methods
A wide literature search of the PubMed/MEDLINE, Scopus, Embase and Cochrane library databases was made to find relevant published articles about the diagnostic performance of 18F-FDG PET or PET/CT for the evaluation of IgG4RD.

Results
The comprehensive computer literature search revealed 779 articles. On reviewing the titles and abstracts, 756 articles were excluded because the reported data were not within the field of interest. Twenty-three studies were included in the review.

Conclusion
Despite some limitations that affect our review, 18F-FDG PET or PET/CT demonstrated the ability to assess IgG4RD both at initial evaluation and after therapy. In general, no correlation between PET/CT parameters and IgG4 serum levels has been reported. A possible role for 18F-FDG PET/CT to drive differential diagnosis with other disease is starting to emerge.
Hemiarthroplasty in complex proximal humeral fractures: preserving unity of the tuberosities with the cap technique improves clinical outcome
Authors: Putzeys Guy , Uyttebroek Sigurd 
Published: April 2022

Abstract

Objectives:
The outcome of primary hemiarthroplasty for complex proximal humeral fractures is highly dependent on the position and survival of the tuberosities. Preserving the cuff–tuberosity complex as a unit (named cap technique) is thought to improve the reduction and stability of the tuberosities. We present the first report of the cap technique and compare it with the common intertubercular split technique.

Design:
Comparative retrospective study on consecutive patients

Setting:
Urban level 1 trauma center.

Patients/Participants:
Included were all patients treated between May 2010 and August 2019 with the Affinis Fracture (Mathys, Switzerland) hemiarthroplasty for complex shoulder fractures. The cap technique was used from February 2015 onward. Minimum follow-up of 11 months. Dementia was an exclusion criterium.

Outcome Measure:
Clinical evaluation by (normalized) Constant-Murley score, DASH score, and EQ5D-VAS score. Radiological outcomes according to the criteria of Boileau.

Results:
The cap-technique group consisted of 26 patients. One patient had revision surgery; 23 patients could be evaluated at a mean follow-up of 28 months. The control group consisted of 26 patients. Three patients had revision surgery. Ten patients could be scored at a mean follow-up of 101 months. A statistically significant difference in Constant-Murley score (P = .0121) could be observed between case and control group. There were no significant differences between radiological scores and between revision rates.

Conclusion:
The cap technique significantly improves clinical outcome in comparison with the intertubercular split technique. However, there was no significant difference in radiographic appearance of the tuberosities.
Does the accuracy of prehospital pelvic binder placement affect cardiovascular physiological parameters during rescue? A clinical study in patients with pelvic ring injuries
Authors: Tiziani Simon , Janett Anna–Staschia , Alkadhi Hatem , Osterhoff Georg , Sprengel Kai , Pape Hans–Christoph 
Published: April 2022

Abstract

Introduction:
Pelvic binders (PB) have become an established first–line treatment for on scene use in suspected pelvic ring injuries. A sustained incidence of incorrect placements was reported, usually above the trochanteric region. We examined if malplacement is associated with worse clinical parameters related to resuscitation.

Methods:
Retrospective chart review, level 1 center over a 3–year period. Inclusion criteria: adult patients (18–69y/o), high–energy injury, presence of a pelvic binder on admission — patients without binders served as controls. Exclusions: geriatric patients (>70y/o), ground level falls. Malplacement of the binder was assessed and graded (grade 1:<5 cm above trochanter, grade 2:5–10 cm, grade 3 > 10 cm) from the initial computed tomography scan (3D reconstruction).

Results:
Seventy–six patients were included. Males (72%), mean age 47years (range 18–91, SD 19.4). Mean Injury Severity Score was 22.3 points (range 1 –48, SD 10.4) and mean Glasgow Coma Score on arrival was 10.8 points (range 3–15, SD 5.3). Fifty-three percent presented with a pelvic ring injury (74% of them with a type B or C fracture). Mean PB distance from the trochanteric region was 56 mm (range 41–247 mm, SD 54.5). Fifty percent of PBs were moderately displaced, 21% showed severe misplacement (>100 mm). Physiological parameters were unchanged regardless of the accuracy of PB placement.

Conclusion:
Incorrect placement of pelvic binders persists despite widespread implementation of the device. In our series, displacement was always cranially and had no effect on preclinical fluids received or parameters of resuscitation on arrival.

Level of Evidence:
III
Outcome of geriatric proximal humeral fractures: a comparison between reverse shoulder arthroplasty versus open reduction and internal fixation
Authors: Ott Nadine , Müller Carolin , Jacobs Andreas , Paul Christian , Wegmann Kilian , Müller Lars Peter , Kabir Koroush 
Published: April 2022

Abstract

Objectives:
In view of the increased attention to reverse shoulder arthroplasty (rTSA) as a treatment for complex proximal humeral fractures in the elderly, the present study analyzes in-hospital complications and the postoperative management of rTSA versus open reduction and internal fixation (ORIF).

Methods:
We retrospectively reviewed patients hospitalized from 2016 to 2018 for proximal humeral fractures (ICD-9 codes: S42.21), III- and IV-part, who underwent an ORIF with locking plates, rTSA or nonoperative treatment. In-hospital complications and postoperative management in both groups were included in the analysis.

Results:
We included n 190 patients (ORIF 90, rTSA 71, nonoperative 29), more likely to be female (82.1% vs 17.9%; P
< .01) with an average age of 82years (min. 72, max. 99; SD 6.4). The ORIF and the rTSA groups showed comparable complication rates (15.6% vs 15%, P
= .87) but with a significantly shorter hospital stay (8.6 vs 11.5days; P
= .01) and shorter duration of surgery (72.9 vs 87.2 minutes; P
= .01) in the ORIF group. Significantly more patients after ORIF achieved an independent life postoperatively (53.3% vs 40.8%; P
= .013).

Conclusions:
In this retrospective analysis, ORIF is related to a shorter duration of surgery, a shorter hospital stay and a higher likelihood of independence. Despite the popularity of the rTSA, ORIF remains a reliable treatment option for proximal humeral fractures in the elderly.
Level of evidence: III