bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjunctive sepsis therapy with aminophylline (STAP): a randomized controlled trial
Authors: Zhang Ruifang , Liu Huan , Dai Dongmei , Ding Xianfei , Wang Dong , Wang Yan , Shi Xuexiu , Zhang Shuguang , Duan Xiaoguang , Wang Haixu , Luo Yonggang , Liu Shaohua , Han Bing , Zhang Xiaojuan , Fang Yu , Xu Wangbin , Sun Tongwen 
Published: April 2021

Abstract
BackgroundSepsis is a serious disease that is often caused by infection. Aminophylline has anti-asthma and anti-inflammatory effects. We aimed to explore the safety and effect of aminophylline in sepsis.MethodsWe conducted a clinical randomized controlled trial involving 100 patients diagnosed with sepsis within 48 hours after ICU (intensive care unit) admission in two sites (First Affiliated Hospital of Zhengzhou University and First Affiliated Hospital of Kunming Medical University). All patients were randomized in a 1:1 ratio to receive standard therapy with or without aminophylline. The primary clinical outcome was all-cause mortality at 28 days.ResultsFrom 27 September 2018 to 12 February 2020, we screened 277 septic patients and eventually enrolled 100 patients, with 50 assigned to the aminophylline group and 50 to the usual-care group. At 28 days, 7 of 50 patients (14.0%) in the aminophylline group had died, compared with 16 of 50 (32.0%) in the usual-care group (P = 0.032). Cox regression showed that the aminophylline group had a lower risk of death (HR = 0.312, 95%CI: 0.129–0.753). Compared with the usual-care group, patients in the aminophylline group had a longer survival time (P = 0.039 by the log-rank test). With the extension of the treatment time, the effect of aminophylline on the doses of vasopressors, oxygenation index, and SOFA score increased. There were no significant differences in total hospitalization days, ICU hospitalization days, and rates of serious adverse events (all P > 0.05). No adverse events were observed in the trial.ConclusionsAminophylline as an adjunct therapy could significantly reduce the risk of death and prolong the survival time of patients with sepsis.Trial registrationThe trial was registered at the Chinese clinical trial registry (ChiCTR1800019173), 29 October 2018 - retrospectively registered, http://www.chictr.org.cn/index.aspx
Characteristics of the ideal hospitalist inpatient care program: perceptions of Canadian health system leaders
Authors: Yousefi Vandad , McIvor Elayne 
Published: April 2021

Abstract
Background: Despite the growing prevalence of hospitalist programs in Canada, it is not clear what program features are deemed desirable by administrative and medical leaders who oversee them. We aimed to understand perceptions of a wide range of healthcare administrators and frontline providers about the necessary characteristics of a hospitalist service. Methods: We conducted semi-structured interviews with a range of administrators, medical leaders and frontline providers across three hospital sites in an integrated health system in Western Canada. Results: Most interviewees identified the hospitalist model as the ideal inpatient care service line, but identified a number of challenges. Interviewees identified the necessary features of an ideal hospitalist service to include considerations for program design, care and non-clinical processes, and alignment between workload and physician staffing. Conclusions: Most hospital administrators and frontline providers in our study believed the hospitalist model resulted in improvements in clinical processes and work environment.
Demographic Characteristics, Clinical and Laboratory Features, and The Distribution of Pathogenic Variants In the Cftr Gene In the Cypriot Cystic Fibrosis (Cf) Population Demonstrate The Utility of a National Cf Patient Registry
Authors: Yiallouros Panayiotis K. , Matthaiou Andreas M. , Anagnostopoulou Pinelopi , Kouis Panayiotis , Libik Malgorzata , Adamidi Tonia , Eleftheriou Adonis , Demetriou Artemios , Ioannou Phivos , Tanteles George A. , Costi Constantina , Fanis Pavlos , Macek Milan , Neocleous Vassos , Phylactou Leonidas A. 
Published: April 2021

Abstract
Background

Specialized clinical care for cystic fibrosis (CF) in Cyprus, a small island country, has been implemented since the 1990s. However, only recently, a national CF patient registry has been established for the systematic recording of patients’ data. In this study, we aim to present data on the epidemiological, genotypic and phenotypic features of CF patients in the country from the most recent data collection in 2019, with particular emphasis on notable rare or unique cases.
Results

Overall, data from 52 patients are presented, 5 of whom have deceased and 13 have been lost to follow-up in previous years. The mean age at diagnosis was 7.2 ± 12.3 years, and the mean age of 34 alive patients by the end of 2019 was 22.6 ± 13.2 years. Patients most commonly presented at diagnosis with acute or persistent respiratory symptoms (46.2%), failure to thrive or malnutrition (40.4%), and dehydration or electrolyte imbalance (32.7%). Sweat chloride levels were diagnostic (above 60 mmol/L) in 81.8% of examined patients. The most common identified mutation was p.Phe508del (F508del) (45.2%), followed by p.Leu346Pro (L346P) (6.7%), a mutation detected solely in individuals of Cypriot descent. The mean BMI and FEV1 z-scores were 0.2 ± 1.3 and − 2.1 ± 1.7 across all age groups, respectively, whereas chronic Pseudomonas aeruginosa colonization was noted in 26.9% of patients. The majority of patients (74.5%) were eligible to receive at least one of the available CFTR modulator therapies. In 25% of patients we recovered rare or unique genotypic profiles, including the endemic p.Leu346Pro (L346P), the rare CFTR-dup2, the co-segregated c.4200_4201delTG/c.489 + 3A > G, and the polymorphism p.Ser877Ala.
Conclusions

CF patient registries are particularly important in small or isolated populations, such as in Cyprus, with rare or unique disease cases. Their operation is necessary for the optimization of clinical care provided to CF patients, enabling their majority to benefit from evolving advances in precision medicine.
TFE3 Regulates the Function of Autophagy-Lysosome to Drive&nbsp;Invasion and Metastasis of Papillary Thyroid Carcinoma
Authors: Lu Hongsheng , Zhu Chumeng , Ruan Yanyun , Fan Lilong , Wei Kena , Chen Qi , Wei Qing 
Published: April 2021

Abstract
Background: Cumulatively, evidence shows that autophagy plays an important role in the occurrence, development, and metastasis of tumors, and even determines the prognosis of tumors. However, little is known about its role in papillary thyroid carcinoma and TFE3 as a potential oncogene in regulating autophagy lysosome.Methods: Immunohistochemistry and real-time quantitative PCR (qRT‐PCR) assays were used to examine the expression of TFE3, P62/SQSTM1 and LC3 in PTC tissues and para-cancer tissues. TFE3, P62/SQSTM1, and LC3 were evaluated using Western blot assay. After inducing TFE3 overexpression by plasmid or TFE3 downregulation by small interfering RNA (siRNA) transfection, MTT, Wound healing assay, Cell migration and invasion assays were used to verify the effects on invasion, migration and autophagy-lysosome related proteins such as P62/SQSTM1 and LC3.Results: The TFE3, P62/SQSTM1, and LC3 in PTC tissues were overexpression than that in para-cancer tissues. Analysis of clinicopathological characteristics in PTC patients showed that high expression of TFE3 was significantly correlated with lymph node metastasis. Overexpression of TFE3 in the PTC cell lines KTC-1 and BCPAP promoted PTC cells proliferation, invasion, and migration. Knockdown of TFE3 had the opposite effect. Furthermore, we found a positive relationship between TFE3 with P62/SQSTM1 and LC3 expression, and silencing TFE3 inhibited P62/SQSTM1 and LC3 expression in PTC cells. Meanwhile, overexpression of TFE3 had the opposite effect. Conclusions: The present study provided the evidence of the underlying mechanisms of TFE3 in inducing the function of autophagy-lysosome of papillary thyroid carcinoma and implicated the potential application of TFE3 as a sensitive marker of PTC lymph node metastasis.
Clinical quality strategy to assess data integrity of germline variants inferred from tumor-only testing sequencing data
Authors: Ménard Timothé , Rolo Donato , Koneswarakantha Björn 
Published: April 2021

Abstract
In the majority of cancers, pathogenic variants are only found at the level of the tumor; however, an unusual number of cancers and/or diagnoses at an early age in a single family may suggest a genetic predisposition. Predisposition plays a major role in about 5 to 10% of adult cancers and in certain childhood tumors. As access to genomic testing for cancer patients continues to expand, the identification of Potential Germline Pathogenic Variants (PGPV) through tumor-DNA sequencing is also increasing. Statistical methods have been developed to infer the presence of a PGPV without the need of a matched normal sample. These methods are mainly used for exploratory research, for example in real-world Clinico-Genomic Databases/platforms (CGDB). These databases are being developed to support many applications such as targeted drug development, clinical trial optimization and post marketing studies. To ensure the integrity of data used for research, a Quality Management System (QMS) should be established, and Quality Oversight Activities (QOAs) should be conducted to assess and mitigate clinical quality risks (for patient safety and data integrity). As opposed to well-defined GxP areas such as Good Clinical Practice (GCP), there are no comprehensive instructions on how to assess the clinical quality of statistically derived variables from sequencing data such as PGPV. In this report, we aim to share our strategy and propose a possible set of tactics to assess the PGPV quality and to ensure data integrity in exploratory research.
Clinical and Bacteriological features of spontaneous bacterial peritonitis in Malagasy patients with Cirrhosis
Authors: Rakotozafindrabe Andry Lalaina Rinà , Razafindrazoto Chantelli Iamblaudiot , Rasolonjatovo Anjaramalala Sitraka , Lantonirina Jean Désiré Ezra , Rakotomalala Jolivet Auguste , Randriamifidy Nitah Harivony , Maherison Sonny , Ralaizanaka Behoavy Mahafaly , Rabenjanahary Tovo Harimanana , Ramanampamonjy Rado Manitrala 
Published: April 2021

Abstract
Background: Spontaneous bacterial peritonitis (SBP) represent frequent and serious complications in cirrhosis patients with ascites. Our aim was to describe the clinical and bacteriological characteristics of SBP in Madagascar.Methods: This is a 21-month prospective study between January 2018 and October 2019, including hospitalized patients with cirrhosis, with clinical and biological symptoms of SBP.Results: Thirty-three patients were included. The mean age was 48.09 ± 13.55 years (extremes: 19 – 78 years), the sex ratio was 3.12. Abdominal pain (55%), fever (36%), diarrhea (6%), hepatic encephalopathy (18%) are the most common symptoms. Gastrointestinal bleeding (18.18%) was the main risk factor to SBP. SBP was community-acquired in 87.88% of cases. A culture of ascites fluid was positive for 9 patients (27.27%). The infectious agents found were Escherichia coli (12.10%), Klebsiella pneumoniae (3%), Pseudomonas (3%), Streptococcus mitis (9.1%). Escherichia coli were wild with one case resistant to Ceftriaxone. The Klebsiella were multidrug resistant. The other two pathogens did not show resistance. After antibiotic therapy adapted to the antibiogram, healing was observed in 26 patients (78.78%). Seven patients (21.22%) died from various complications. All deceased patients had bacteria identified in ascites fluid.Conclusion: SBP defined according to clinical and biological criteria is apparently sterile in the majority of cases. Gram-negative bacteria were the major pathogens involved in SBP in cirrhotic patients. Escherichia coli and streptococcus were the most common pathogen isolated. Bacteriological study is essential to adapt antimicrobial to multidrug-resistant bacteria.
The influence of prophylactic Calcium- and Magnesium supplementation on postoperative hypocalcemia after total thyroidectomy: study protocol for a randomized controlled trial
Authors: Tabriz Navid , Fried Dennis , Uslar Verena Nicole , Weyhe Dirk 
Published: April 2021

Abstract
• BackgroundWe want to investigate if a routine preoperative dietary supplementation of calcium and magnesium prior to thyroidectomy for nodular goiter and grave´s disease can influence patients’ outcome with regards to hypocalcemia associated symptoms and quality of life in order to reduce the risk of post-thyroidectomy hypocalcemia and to improve patient`s quality of life.• MethodsThe study will be conducted as a two-armed randomized controlled trial with patients scheduled for total thyroidectomy. The patients assigned to the intervention group will receive calcium carbonate and magnesium oxide, and will begin the intake 2 weeks preoperatively. Primary outcome is the postoperative quality of life measured by using the ThyPRO-39 and EQ-5D questionnaires. Secondary outcome is the assessment of postoperative biochemical (calcium and PTH levels) and clinical hypocalcemia (symptoms as reported by the patient).• DiscussionA prophylactic dietary substitution with calcium and magnesium, which could easily be done in the preoperative setting, could potentially help to avoid or reduce hypocalcemia-associated symptoms and improve quality of life. In the event of a positive outcome, this preoperative procedure can be an inexpensive way to prepare patients scheduled for thyroidectomy and can possibly reduce disease-specific costs by reducing the postoperative complication rate.• Trial registration: DRKS00017195 in the German clinical trials register (Deutsches Register Klinischer Studien, DRKS) on the 22.05.2019.
Wpływ błędu i ignorancji co do istoty aktu prawnego na jego nieważność (kan. 126 KPK)
Authors: DZIERŻON KS. GINTER 
Published: April 2021

W prezentowanym artykule przedmiotem uwagi Autora stała się interpretacja kan. 126 KPK dotyczącego wpływu błędu i ignorancji co do istoty aktu prawnego na jego nieważność. Wykazał on, iż błąd i ignorancja są autonomicznymi wadami aktu prawnego. W zakończeniu opracowania polemizując z poglądem Winfrieda Aymansa i Klausa Mörsdorfa stojącymi na stanowsiku, iż pomiędzy kan. 125 § 2 KPK w którym skodyfikowano wpływ podstępu i bojaźni na ważność aktu prawnego i kan. 126 KPK istnieje pewien brak równowagi wyraził on pogląd, iż takie twierdzenie jest nieuprawnione. Zdaniem Autora o skodyfikowaniu tych zasad zadecydowaly inne racje. Twierdzi on, iż w kan. 125 § 2 KPK prawodawca stworzył możłiwość rozwiązania aktu, ponieważ uznał, że w tym wypadku została naruszona zasada sprawiedliwości. Tym sposobem pragnie on chronić tych, którzy zostali pokrzywdzeni.
W opinii Autora, inny powód zadecydował natomiast o wprowadzeniu zasady skodyfkowanej w kan. 126 KPK. W tym wypadku zadecydowały o tym racje teoretycznoprawne o podłożu ontologicznym w rozumieniu filozoficznym arystotelesowsko-tomistycznym. W jego przekonaniu, zniekształcenie przedmiotu aktu w jego elementach istotnych będące następstwem błędu (ignorancji) substancjalnego z natury rzeczy nie może generować innych następstw, jak tylko nieważność aktu prawnego.
Odnowa duszpastersko-religijna w diecezji włocławskiej w świetle uchwał synodalnych biskupa Macieja Łubieńskiego (1631-1641)
Authors: GRĘŹLIKOWSKI KS. JANUSZ 
Published: April 2021

Dar reformy i odnowy duszpasterskiej ofiarowany Kościołowi połowy XVI wieku w uchwałach Soboru Trydenckiego, realizowany i wprowadzany w życie Kościołów partykularnych przez kolejne wieki, został gorliwie i owocnie podjęty przez biskupa Macieja Łubieńskiego i to z wielkim rozmachem na trzech synodach, dwóch diecezjalnych w 1634 i 1641 r. oraz na synodzie odbytym dla archidiakonatu pomorskiego w 1640 r. Ich uchwały stały się nie tylko okazją do przeprowadzenia odnowy duszpasterskiej Kościoła włocławskiego, ale także przyczyniły się do pogłębienia znajomości i szacunku dla prawa oraz stały się skutecznym instrumentem do zachowania jedności i karności kościelnej w diecezji, jak też wprowadzania reformy trydenckiej. Osadzone mocno w dekretach soborowych oraz statutach prowincjonalnych uchwały synodów normowały wiele sektorów życia duszpasterskiego ówczesnej diecezji kujawsko-pomorskiej, uaktywniając samych duszpasterzy, jak i angażując religijnie i moralnie wiernych świeckich. Ten wybitny ustawodawca, reformator i zwolennik odnowy trydenckiej Kościoła i jego struktur duszpasterskich, zdawał sobie sprawę, że odnowa duszpasterstwa i naprawa życia religijno-moralnego musi znaleźć swój początek w reformie duchowieństwa, zachowaniu karności i dyscypliny kościelnej oraz w życiu i postępowaniu duchownych zgodnym z duchem powołania kapłańskiego. Uchwały synodalne biskupa Łubieńskiego były przejawem jego gorliwości ustawodawczo – reformistycznej. Usilnie zabiegał o ujednolicenie przepisów prawnych odnoszących się do życia sakramentalnego, dyscypliny duchowieństwa oraz rozwoju życia religijnego, a jednocześnie rozwoju duszpasterstwa. Jego działalność ustawodawcza i prawno-duszpasterska była w miarę usystematyzowana, szeroka i całościowa. Odnosiła się bowiem najpierw do działalności czysto ustawodawczej, a także miała charakter praktyczny, gdyż odnosiła się i służyła odnowie duszpasterstwa i życia religijnego wiernych.
Odnowie duszpasterstwa służyły też podejmowane wysiłki zmierzające do usprawnienia organizacji dekanatów oraz ożywienie działalności dziekanów, m.in. w zakresie kontroli duszpasterstwa, przypominania proboszczom ich powinności w zakresie poznawania parafian, opieki nad chorymi i ubogimi, zarządzenia odnoszące się do obrony wiary katolickiej zagrożonej reformacją, regulacje odnoszące się do nauczania prawd wiary, nauczania katechetycznego, sprawowania i przyjmowania sakramentów, kultu Bożego i spraw liturgicznych. To wszystko miało służyć posoborowej odnowie duszpasterstwa w diecezji włocławskim.
Genetic and Epigenetic Biomarkers for Diagnosis, Prognosis and Treatment of Metabolic Syndrome
Authors: Giglio Rosaria V. , Stoian Anca P. , Patti Angelo M. , Rizvi Ali A. , Sukhorukov Vasily , Ciaccio Marcello , Orekhov Alexander , Rizzo Manfredi 
Published: April 2021

Background:
Metabolic syndrome is a clinical condition that deserves special attention because it
puts the individual at high cardiovascular risk, especially heart attack and stroke. Considering precision
medicine, it would be advisable to evaluate the individual cardio-metabolic risk by estimating the coexistence
of risk factors (abdominal obesity, low level of High-Density Lipoprotein Cholesterol, High Triglycerides, and
small dense Low-Density Lipoproteins sub-classes, hypertension, and elevated fasting glycemia), which could
engrave on metabolism increasing cardiovascular mortality.

Objective:
To identify genetic and epigenetic biomarkers may assist in the possibility of helping follow-up
strategies and other measures of prevention and in metabolic risk.

Methods:
We searched for studies that valued the combination between epigenetic biomarkers and all factors of
cardio-metabolic risk.

Results:
Numerous researches have investigated the molecular start of metabolic alterations, focusing on the
epigenetic mark, as methylation of DNA, histone modifications and non.coding RNAs. It has been found that
DNA methylation is the most searched epigenetic sign in the human genome concerning the control of gene expression.

Conclusion:
For the screening, diagnosis, and prognosis of metabolic syndrome and the prescription of personalized
medicine, the DNA methylation biomarkers specify for subjects have been recognized as an ensuring
tool. While these results are promising, further investigations are needed to unravel the complicated synergic association
of the genome, epigenome and the situations related to metabolic pathology.
Nutraceuticals with Anti-inflammatory and Anti-oxidant Properties as an
Intervention for Reducing the Health Effects of Fine Particulate Matter:
Potential and Prospects
Authors: Rana Sindhuprava , Trushna Tanwi , Tripathi Amit K. , Tiwari Rajnarayan R. 
Published: April 2021

:
Air pollution, especially particulate matter pollution, adversely affects human health. A
growing pool of evidence has emerged which underscores the potential of individual-level
nutritional interventions in attenuating the adverse health impact of exposure to PM2.5. Although
controlling emission and reducing the overall levels of air pollution remains the ultimate objective
globally, the sustainable achievement of such a target and thus consequent protection of human
health will require a substantial amount of time and concerted efforts worldwide. In the meantime,
smaller-scale individual-level interventions that can counter the inflammatory or oxidative stress
effects triggered by exposure to particulate matter may be utilized to ameliorate the health effects
of PM2.5 pollution. One such intervention is the incorporation of nutraceuticals in the diet. Here,
we present a review of the evidence generated from various in vitro, in vivo and human studies
regarding the effects of different anti-inflammatory and antioxidant nutraceuticals in ameliorating
the health effects of particulate matter air pollution. The studies discussed in this review suggest
that these nutraceuticals, when consumed as a part of the diet or as additional supplementation,
can potentially negate the cellular level adverse effects of exposure to particulate pollution. The
potential benefits of adopting a non-pharmacological diet-based approach to air pollution-induced
disease management have also been discussed. We argue that before a nutraceuticals-based
approach can be used for widespread public adoption, further research, especially human clinical
trials, is essential to confirm the beneficial action of relevant nutraceuticals and to explore the safe
limits of human supplementation and the risk of side effects. Future research should focus on
systematically translating bench-based knowledge regarding nutraceuticals gained from in vitro
and in vivo studies into clinically usable nutritional guidelines.