bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving time to palliative care review with predictive modeling in an inpatient adult population: study protocol for a stepped-wedge, pragmatic randomized controlled trial
Authors: Wilson Patrick M. , Philpot Lindsey M. , Ramar Priya , Storlie Curtis B. , Strand Jacob , Morgan Alisha A. , Asai Shusaku W. , Ebbert Jon O. , Herasevich Vitaly D. , Soleimani Jalal , Pickering Brian W.
Published: September 2021

Background

Palliative care is a medical specialty centered on improving the quality of life (QOL) of patients with complex or life-threatening illnesses. The need for palliative care is increasing and with that the rigorous testing of triage tools that can be used quickly and reliably to identify patients that may benefit from palliative care.

Methods

To that aim, we will conduct a two-armed stepped-wedge cluster randomized trial rolled out to two inpatient hospitals to evaluate whether a machine learning algorithm accurately identifies patients who may benefit from a comprehensive review by a palliative care specialist and decreases time to receiving a palliative care consult in hospital. This is a single-center study which will be conducted from August 2019 to November 2020 at Saint Mary’s Hospital & Methodist Hospital both within Mayo Clinic Rochester in Minnesota. Clusters will be nursing units which will be chosen to be a mix of complex patients from Cardiology, Critical Care, and Oncology and had previously established relationships with palliative medicine. The stepped wedge design will have 12 units allocated to a design matrix of 5 treatment wedges. Each wedge will last 75 days resulting in a study period of 12 months of recruitment unless otherwise specified. Data will be analyzed with Bayesian hierarchical models with credible intervals denoting statistical significance.

Discussion

This intervention offers a pragmatic approach to delivering specialty palliative care to hospital patients in need using machine learning, thereby leading to high value care and improved outcomes. It is not enough for AI to be utilized by simply publishing research showing predictive performance; clinical trials demonstrating better outcomes are critically needed. Furthermore, the deployment of an AI algorithm is a complex process that requires multiple teams with varying skill sets. To evaluate a deployed AI, a pragmatic clinical trial can accommodate the difficulties of clinical practice while retaining scientific rigor.

Trial registration

ClinicalTrials.gov NCT03976297. Registered on 6 June 2019, prior to trial start.
Stepped care for depression at integrated chronic care centers (IC3) in Malawi: study protocol for a stepped-wedge cluster randomized controlled trial
Authors: McBain Ryan K. , Mwale Owen , Ruderman Todd , Kayira Waste , Connolly Emilia , Chalamanda Mark , Kachimanga Chiyembekezo , Khongo Brown David , Wilson Jesse , Wroe Emily , Raviola Giuseppe , Smith Stephanie , Coleman Sarah , Kelly Ksakrad , Houde Amruta , Tebeka Mahlet G. , Watson Samuel , Kulisewa Kazione , Udedi Michael , Wagner Glenn
Published: September 2021

Background

Malawi is a low-income country in sub-Saharan Africa that has limited resources to address a significant burden of disease—including HIV/AIDS. Additionally, depression is a leading cause of disability in the country but largely remains undiagnosed and untreated. The lack of cost-effective, scalable solutions is a fundamental barrier to expanding depression treatment. Against this backdrop, one major success has been the scale-up of a network of more than 700 HIV clinics, with over half a million patients enrolled in antiretroviral therapy (ART). As a chronic care system with dedicated human resources and infrastructure, this presents a strategic platform for integrating depression care and responds to a robust evidence base outlining the bi-directionality of depression and HIV outcomes.

Methods

We will evaluate a stepped model of depression care that combines group-based Problem Management Plus (group PM+) with antidepressant therapy (ADT) for 420 adults with moderate/severe depression in Neno District, Malawi, as measured by the Patient Health Questionnaire-9 (PHQ-9) and Mini-International Neuropsychiatric Interview (MINI). Roll-out will follow a stepped-wedge cluster randomized design in which 14 health facilities are randomized to implement the model in five steps over a 15-month period. Primary outcomes (depression symptoms, functional impairment, and overall health) and secondary outcomes (e.g., HIV: viral load, ART adherence; diabetes: A1C levels, treatment adherence; hypertension: systolic blood pressure, treatment adherence) will be measured every 3 months through 12-month follow-up. We will also evaluate the model’s cost-effectiveness, quantified as an incremental cost-effectiveness ratio (ICER) compared to baseline chronic care services in the absence of the intervention model.

Discussion

This study will conduct a stepped-wedge cluster randomized trial to compare the effects of an evidence-based depression care model versus usual care on depression symptom remediation as well as physical health outcomes for chronic care conditions. If determined to be cost-effective, this study will provide a model for integrating depression care into HIV clinics in additional districts of Malawi and other low-resource settings with high HIV prevalence.

Trial registration

ClinicalTrials.govNCT04777006. Registered on 1 March, 2021
Improving sustainable hydrogen production from green waste: [FeFe]-hydrogenases quantitative gene expression RT-qPCR analysis in presence of autochthonous consortia
Authors: Arizzi M. , Morra S. , Gilardi G. , Pugliese M. , Gullino M. L. , Valetti F.
Published: September 2021

Background

Bio-hydrogen production via dark fermentation of low-value waste is a potent and simple mean of recovering energy, maximising the harvesting of reducing equivalents to produce the cleanest fuel amongst renewables. Following several position papers from companies and public bodies, the hydrogen economy is regaining interest, especially in combination with circular economy and the environmental benefits of short local supply chains, aiming at zero net emission of greenhouse gases (GHG). The biomasses attracting the largest interest are agricultural and urban green wastes (pruning of trees, collected leaves, grass clippings from public parks and boulevards), which are usually employed in compost production, with some concerns over the GHG emission during the process. Here, an alternative application of green wastes, low-value compost and intermediate products (partially composted but unsuitable for completing the process) is studied, pointing at the autochthonous microbial consortium as an already selected source of implementation for biomass degradation and hydrogen production. The biocatalysts investigated as mainly relevant for hydrogen production were the [FeFe]-hydrogenases expressed in Clostridia, given their very high turnover rates.

Results

Bio-hydrogen accumulation was related to the modulation of gene expression of multiple [FeFe]-hydrogenases from two strains (Clostridium beijerinckii AM2 and Clostridium tyrobutyricum AM6) isolated from the same waste. Reverse Transcriptase quantitative PCR (RT-qPCR) was applied over a period of 288 h and the RT-qPCR results showed that C. beijerinckii AM2 prevailed over C. tyrobutyricum AM6 and a high expression modulation of the 6 different [FeFe]-hydrogenase genes of C. beijerinckii in the first 23 h was observed, sustaining cumulative hydrogen production of 0.6 to 1.2 ml H2/g VS (volatile solids). These results are promising in terms of hydrogen yields, given that no pre-treatment was applied, and suggested a complex cellular regulation, linking the performance of dark fermentation with key functional genes involved in bio-H2 production in presence of the autochthonous consortium, with different roles, time, and mode of expression of the involved hydrogenases.

Conclusions

An applicative outcome of the hydrogenases genes quantitative expression analysis can be foreseen in optimising (on the basis of the acquired functional data) hydrogen production from a nutrient-poor green waste and/or low added value compost, in a perspective of circular bioeconomy.
Characterization of fatty acid desaturases reveals stress-induced synthesis of C18 unsaturated fatty acids enriched in triacylglycerol in the oleaginous alga Chromochloris zofingiensis
Authors: Wu Tao , Yu Lihua , Zhang Yu , Liu Jin
Published: September 2021

Background

The green microalga Chromochloris zofingiensis is capable of producing high levels of triacylglycerol rich in C18 unsaturated fatty acids (UFAs). FA desaturation degree is regulated by FA desaturases (FADs). Nevertheless, it remains largely unknown regarding what FADs are involved in FA desaturations and how these FADs collaborate to contribute to the high abundance of C18 UFAs in triacylglycerol in C. zofingiensis.

Results

To address these issues, we firstly determined the transcription start sites of 11 putative membrane-bound FAD-coding genes (CzFADs) and updated their gene models. Functional validation of these CzFADs in yeast and cyanobacterial cells revealed that seven are bona fide FAD enzymes with distinct substrates. Combining the validated functions and predicted subcellular compartments of CzFADs and the FA profiles of C. zofingiensis, the FA desaturation pathways in this alga were reconstructed. Furthermore, a multifaceted lipidomic analysis by systematically integrating thin-layer chromatography, gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry techniques was conducted, unraveling profiles of polar membrane lipids in C. zofingiensis and major desaturation steps occurring in these lipids. By correlating transcriptional patterns of CzFAD genes and changes of lipids upon abiotic stress conditions, our results highlighted collaboration of CzFADs for C18 UFA synthesis and supported that both de novo FA synthesis and membrane lipid remodeling contributed C18 UFAs to triacylglycerol for storage.

Conclusions

Taken together, our study for the first time elucidated the pathways of C18 FA desaturations and comprehensive profiles of polar membrane lipids in C. zofingiensis and shed light on collaboration of CzFADs for the synthesis and enrichment of C18 UFAs in triacylglycerol.
Impact of molecular surgical margin analysis on the prediction of pancreatic cancer recurrences after pancreaticoduodenectomy
Authors: Sunagawa Yuki , Hayashi Masamichi , Yamada Suguru , Tanabe Hiroshi , Kurimoto Keisuke , Tanaka Nobutake , Sonohara Fuminori , Inokawa Yoshikuni , Takami Hideki , Kanda Mitsuro , Tanaka Chie , Nakayama Goro , Koike Masahiko , Kodera Yasuhiro
Published: September 2021

Background

Pancreatic cancer is one of the lethal cancers among solid malignancies. Pathological diagnosis of surgical margins is sometimes unreliable due to tissue shrinkage, invisible field cancerization and skipped lesions like tumor budding. As a result, tumor recurrences sometimes occur even from the pathologically negative surgical margins.

Methods

We applied molecular surgical margin (MSM) analysis by tissue imprinting procedure to improve the detection sensitivity of tiny cancerous cells on the surgical specimen surface after pancreatoduodenectomy. Surgical specimens were collected from 45 pancreatic cancer cases who received subtotal stomach preserving pancreatoduodenectomy at Nagoya University Hospital during 2017–2019. Quantitative methylation-specific PCR (QMSP) of the original methylation marker panel (CD1D, KCNK12, PAX5) were performed and analyzed with postoperative survival outcomes.

Results

Among 45 tumors, 26 cases (58%) were QMSP-positive for CD1D, 25 (56%) for KCNK12 and 27 (60%) for PAX5. Among the 38 tumors in which at least one of the three markers was positive, CD1D-positive cancer cells, KCNK12-positive cancer cells, and PAX5-positive cancer cells were detected at the surgical margin in 8 cases, 7 cases and 10 cases, respectively. Consequently, a total of 17 patients had at least one marker detected at the surgical margin by QMSP, and these patients were defined as MSM-positive. They were associated with significantly poor recurrence-free survival (p = 0.002) and overall survival (p = 0.005) than MSM-negative patients. Multivariable analysis showed that MSM-positive was the only significant independent factor for worse recurrence-free survival (hazard ratio: 3.522, 95% confidence interval: 1.352–9.179, p = 0.010). On the other hand, a significant proportion of MSM-negative cases were found to have received neoadjuvant chemotherapy (p = 0.019).

Conclusion

Pancreatic cancer-specific methylation marker panel was established to perform MSM analysis. MSM-positive status might represent microscopically undetectable cancer cells on the surgical margin and might influence the postoperative long-term outcomes.
Generalized proportional fractional integral functional bounds in Minkowski’s inequalities
Authors: Aljaaidi Tariq A. , Pachpatte Deepak B. , Shatanawi Wasfi , Abdo Mohammed S. , Abodayeh Kamaleldin
Published: September 2021

In this research paper, we improve some fractional integral inequalities of Minkowski-type. Precisely, we use a proportional fractional integral operator with respect to another strictly increasing continuous function ψ. The functions used in this work are bounded by two positive functions to get reverse Minkowski inequalities in a new sense. Moreover, we introduce new fractional integral inequalities which have a close relationship to the reverse Minkowski-type inequalities viaψ-proportional fractional integral, then with the help of this fractional integral operator, we discuss some new special cases of reverse Minkowski-type inequalities through this work. An open issue is covered in the conclusion section to extend the current findings to be more general.
Efficacy of combination of venetoclax with azacitidine or chemotherapy in refractory/relapse acute leukemias of ambiguous lineage, not otherwise specified
Authors: Liu Kaiqi , Li Yan , Qiu Shaowei , Zhou Chunlin , Wei Shuning , Lin Dong , Zhang Guangji , Wei Hui , Wang Ying , Liu Bingcheng , Gong Xiaoyuan , Fang Qiuyun , Song Yang , Wang Huijun , Li Chengwen , Li Qinghua , Wu Lihua , Gong Benfa , Liu Yuntao , Wang Jianxiang , Mi Yingchang
Published: September 2021

Acute leukemias of ambiguous lineage, not otherwise specified (ALAL-NOS) is a rare type of acute leukemia. Management of relapse/refractory (R/R) patients is still challenging.traditional chemotherapy treatment is not effective. In this paper, we reported 6 R/R patients diagnosed as ALAL-NOS in our hospital, who were treated with venetoclax based treatment (venetoclax combining with azacitidine or chemotherapy). All 6 patients achieved CR. Five of the six patients received allo-HSCT, four patients were still alive in CR until the follow-up day. Our data provide preliminary evidence and show that venetoclax based regimens are effective and safety in patients with R/R ALAL-NOS.
Double defects-induced elastic wave coupling and energy localization in a phononic crystal
Authors: Jo Soo-Ho , Shin Yong Chang , Choi Wonjae , Yoon Heonjun , Youn Byeng D. , Kim Miso
Published: September 2021

This study aims to investigate elastic wave localization that leverages defect band splitting in a phononic crystal with double defects through in-depth analysis of comparison of numerical and experimental results. When more than one defect is created inside a phononic crystal, these defects can interact with each other, resulting in a distinctive physical phenomenon from a single defect case: defect band splitting. For a phononic crystal consisting of circular-hole type unit cells in a thin aluminum plate, under A0 (the lowest antisymmetric) Lamb waves, both numerical simulations and experiments successfully confirm the defect band splitting phenomenon via frequency response functions for the out-of-plane displacement calculated/measured at the double defects within a finite distance. Furthermore, experimental visualization of in-phase and out-of-phase defect mode shapes at each frequency of the split defect bands is achieved and found to be in excellent agreement with the simulated results. Different inter-distance combinations of the double defects reveal that the degree of the defect band splitting decreases with  the increasing distance due to weaker coupling between the defects. This work may shed light on engineering applications of a multiple-defect-introduced phononic crystal, including broadband energy harvesting, frequency detectors, and elastic wireless power transfer.
A case report of fibrolamellar hepatocellular carcinoma, with particular reference to preoperative diagnosis, value of molecular genetic diagnosis, and cell origin
Authors: Takahashi Atsushi , Imamura Hiroshi , Ito Ryota , Kawano Fumihiro , Gyoda Yu , Ichida Hirofumi , Yoshioka Ryuji , Mise Yoshihiro , Fukumura Yuki , Sano Katsuhiro , Saiura Akio
Published: September 2021

Background

Fibrolamellar hepatocellular carcinoma (FL-HCC) is a liver tumor that occurs almost exclusively in young adults without underlying liver disease. In spite of its distinct clinical characteristics and specific imaging findings, preoperative diagnosis is often difficult due to the extremely low incidence of the tumor. Although FL-HCC shows particular morphological features on H&E-stained tissue sections, differential diagnosis from ordinary HCC, especially the scirrhous variant of HCC, and intrahepatic cholangiocarcinoma needs additional immunohistochemical (IHC) analyses and/or molecular genetic testing.

Case presentation

A 21-year-old male patient was referred to our hospital for further evaluation of a large liver mass. Abdominal ultrasound examination, contrast-enhanced computed tomography, and magnetic resonance imaging revealed a well-defined hypervascular lobulated liver mass, 11 × 11 cm in diameter, with a central scar and calcification, in segments 5/8. Under the diagnosis of FL-HCC, we carried out extended anterior sectorectomy, including a part of segment 4. On microscopic examination, the tumor was composed of proliferating polygonal cells with abundant eosinophilic granular cytoplasm containing nuclei with vesicular chromatin and enlarged nucleoli, in an abundant stroma. Collagen fibers arranged in a parallel lamellar pattern were seen in the tumor stroma. These findings, together with the results of subsequent IHC analyses using HAS, CK7, and CD 67, we made the diagnosis of FL-HCC, which was further confirmed by detection of theDNAJB1-PRKACAfusion gene in the tumor cells by RT-PCR.

Conclusion

FL-HCC shows distinct imaging appearances. Although it also has characteristic morphological features, combined use of IHC and/or molecular genetic studies are necessary for the final diagnosis.
Lung transplantation for idiopathic multicentric Castleman disease: potential efficacy and tolerability of a humanized anti-interleukin-6 receptor monoclonal antibody
Authors: Tomioka Yasuaki , Otani Shinji , Tanaka Shin , Shien Kazuhiko , Suzawa Ken , Miyoshi Kentaroh , Yamamoto Hiromasa , Okazaki Mikio , Sugimoto Seiichiro , Yamane Masaomi , Toyooka Shinichi
Published: September 2021

Background

Idiopathic multicentric Castleman disease (iMCD) is a rare polyclonal lymphoproliferative disease caused by the overrepresentation of interleukin-6 (IL-6). Tocilizumab (TCZ) is a humanized monoclonal antibody that binds to the IL-6 receptor and is approved for the treatment of iMCD. The efficacy and tolerability of TCZ in patients with iMCD undergoing lung transplantation (LTx) remain unknown.

Case presentation

We present the case of a 48-year-old iMCD patient with end-stage lung disease (ESLD) who was successfully treated with cadaveric single-LTx. Intravenous TCZ was used to stabilize the iMCD patient every 2 weeks, except for withdrawal immediately after LTx. At 32 month post-transplant, the patient remained asymptomatic without evidence of rejection, development of de novo donor-specific antibody (DSA), and recurrent iMCD in the native lung.

Conclusions

Single-LTx can be a feasible treatment option for ESLD caused by iMCD. TCZ can be used safely and may be beneficial in recipients with iMCD, and TCZ in combination with usual immunosuppression can be helpful in stabilizing iMCD patients pre- and post-LTx.
Urogenital schistosomiasis burden in school-aged children in Tiko, Cameroon: a cross-sectional study on prevalence, intensity, knowledge and risk factors
Authors: Sumbele Irene Ule Ngole , Tabi Doris Bennen , Teh Rene Ning , Njunda Anne Longdoh
Published: September 2021

Background

This study aimed at determining urogenital schistosomiasis (UGS) prevalence, intensity, knowledge and risk factors in school-aged children (SAC) in the new endemic focus of Tiko, Cameroon.

Methods

A cross-sectional study including 389 SAC of both sexes aged 5–15 years was carried out between April and June 2018. A structured questionnaire was used to collect demographic data, clinical and predisposing factors. Urine sample collected was used to detect Schistosoma haematobium eggs by filtration technique and microhaematuria by Heme dipstick COMBI 11. Logistic regression model was used to determine risk factors of UGS.

Results

The overall prevalence of UGS was 37.0% (CI 32.4–41.9) and 32.6% (CI 28.2–37.5) were positive by egg excretion while 24.4% (CI 20.4–28.9) by haematuria. S. haematobium egg excretion and haematuria were significantly higher in males (P = 0.016; P = 0.049) and children 12–15 years old (P = 0.009; P = 0.002), respectively. The mean number of eggs per 10 mL of urine was 77.6 (10.2) and ranged from 2 to 400. The proportion of light intensity of infection was higher (67.7%, CI 59.2–75.2) with no significant differences by sex, age and residence. However, the older children were more heavily infected when compared to the younger children, who had more of light infection. Overall, the mean knowledge score 1.42 (CI 1.32–1.51) on a scale of 6, was poor and the proportion of good knowledge of the disease (23.14%, CI 19.2–27.6) was low. Stream water contact (AOR = 4.94; P = 0.001) was the only significant risk factor identified.

Conclusion

Urogenital schistosomiasis is of public health concern among SAC in Tiko, Cameroon. Most participants have poor knowledge about the disease, hence education on vector-borne diseases and the avoidance of stream water contact should be implemented.
Panitumumab Plus Fluorouracil and Folinic Acid Versus Fluorouracil and Folinic Acid Alone as Maintenance Therapy in RAS Wild-Type Metastatic Colorectal Cancer: The Randomized PANAMA Trial (AIO KRK 0212)
Authors: Modest Dominik Paul , Karthaus Meinolf , Fruehauf Stefan , Graeven Ullrich , Müller Lothar , König Alexander Otto , Fischer von Weikersthal Ludwig , Caca Karel , Kretzschmar Albrecht , Goekkurt Eray , Haas Siegfried , Kurreck Annika , Stahler Arndt , Held Swantje , Jarosch Armin , Horst David , Reinacher-Schick Anke , Kasper Stefan , Heinemann Volker , Stintzing Sebastian , Trarbach Tanja
Published: September 2021

PURPOSE

The randomized PANAMA trial investigated the efficacy of panitumumab (Pmab) when added to maintenance therapy with fluorouracil and folinic acid (FU/FA) in patients with RAS wild-type metastatic colorectal cancer.

METHODS

Following first-line induction therapy with six cycles of FU/FA and oxaliplatin plus Pmab, responding patients (stable disease or partial or complete remission) were randomly assigned (1:1, open-label) to maintenance treatment with either FU/FA plus Pmab or FU/FA alone. The primary objective was to demonstrate superiority of progression-free survival (PFS, time from random assignment until progression or death) in favor of FU/FA plus Pmab with a hazard ratio (HR) of 0.75, a power of 80%, and a significance level of 10%. Secondary end points included overall survival, objective response rate of maintenance therapy, and toxicity. Survival end points were analyzed by the Kaplan-Meier method and compared by log-rank test and Cox regressions. Dichotomous variables were compared by Fisher's exact test; odds ratios were indicated when appropriate. The trial is registered with ClinicalTrials.gov ( NCT01991873 ).

RESULTS

Overall, 248 patients were randomly assigned and received maintenance therapy with either FU/FA plus Pmab (125 patients) or FU/FA alone (123 patients). At data cutoff, with 218 events (of 218 needed), PFS of maintenance therapy was significantly improved with FU/FA plus Pmab (8.8 months v 5.7 months; HR, 0.72; 80% CI, 0.60 to 0.85; P = .014). Overall survival (event rate 54%) numerically favored the FU/FA plus Pmab arm (28.7 months v 25.7 months; HR, 0.84; 95% CI, 0.60 to 1.18; P = .32). Objective response rates were 40.8% in patients receiving FU/FA plus Pmab versus 26.0% in patients receiving FU/FA alone (odds ratio, 1.96; 95% CI, 1.14 to 3.36; P = .02). The most frequent Common Terminology Criteria for Adverse Event grade ≥ 3 event during maintenance therapy was skin rash (7.2%).

CONCLUSION

In RAS wild-type metastatic colorectal cancer, maintenance therapy with FU/FA plus Pmab induced a significantly superior PFS compared with FU/FA alone. If active maintenance therapy is aspired following induction therapy with FU/FA and oxaliplatin plus Pmab, FU/FA plus Pmab appears to be the most favorable option.
Experimental quasi-1D capillary-wave turbulence
Authors: Ricard Guillaume , Falcon Eric
Published: September 2021

Wave turbulence in quasi-1D geometry is usually not investigated experimentally since low-order resonant wave interactions are theoretically prohibited. Here, we report on the first observation of unidirectional capillary-wave turbulence on the surface of a fluid in a canal. We also show that five-wave interactions are the lowest-order resonant process subsisting at small scales, and are thus probably the one generating such quasi-1D capillary wave turbulence. We show that the wave spectrum is compatible with the corresponding dimensional analysis prediction. The main assumptions of weak turbulence theory are also verified experimentally. Quasi-1D wave turbulence could be thus highlighted in other fields of wave turbulence.
Thermally activated dynamics of current-driven skyrmions in random media
Authors: Xiong L. , Jin M. H. , Zheng B.
Published: September 2021

Based on the Landau-Lifshitz-Gilbert equation, we perform large-scale numerical simulations of the skyrmion dynamics with quench disorder at finite temperatures. Two universal creep behaviors are observed below the depinning transition current, and the creep exponents are accurately determined. The thermal rounding exponents at the depinning transition indicate an anisotropic temperature dependence in the perpendicular and parallel directions of the current. Further, the temperature-current phase diagram of the skyrmion Hall angle is builded, and the thermally activated forces are analyzed. Our results provide comprehensive understanding for the role of temperature in the current-driven skyrmion dynamics.
Maternal B cell signaling orchestrates fetal development in mice
Authors: Busse Mandy , Langwisch Stefanie , Tedford Kerry , Fischer Klaus-Dieter , Zenclussen Ana Claudia
Published: September 2021

B cell participation in early embryo/fetal development and the underlying molecular pathways have not been explored. To understand whether maternal B cell absence or impaired signaling interferes with placental and fetal growth, we paired CD19-deficient (CD19−/−) mice, females with B cell-specific MyD88 (BMyD88−/−) or IL10 (BIL10−/−) deficiency as well as wild-type and MyD88−/− controls on C57Bl/6 background with BALB/c males. Pregnancies were followed by ultrasound and Doppler measurements. Implantation number was reduced in BMyD88−/− and MyD88−/− mice. Loss of MyD88 or B cell-specific deletion of MyD88 or IL10 resulted in decreased implantation areas at gestational day (gd) 5, gd8 and gd10, accompanied by reduced placental thickness, diameter and areas at gd10. Uterine artery resistance was enhanced in BIL10−/− dams at gd10. Challenge with 0.4 mg lipopolysaccharide/kg bodyweight at gd16 revealed that BMyD88−/−, BIL10−/− and CD19−/− mothers delivered preterm, whereas controls maintained their pregnancy. B cell-specific MyD88 and IL10 expression is essential for appropriate in utero development. IL10+B cells are involved in uterine blood flow regulation during pregnancy. Finally, B cell-specific CD19, MyD88 and IL10 expression influences susceptibility towards preterm birth.
Clinical Relevance of Gastroesophageal Cancer Associated SNPs for Oncologic Outcome After Curative Surgery
Authors: Jung Jin-On , Wirsik Naita Maren , Nienhüser Henrik , Peters Leila , Müller-Stich Beat Peter , Hess Timo , Schüller Vitalia , Schumacher Johannes , Schmidt Thomas
Published: September 2021

Background

Gastric and esophageal cancers are malignant diseases with rising importance in Western countries. To improve oncologic outcome after surgery, it is essential to understand the relevance of germline mutations. The aim of the study was to identify and distinguish clinically relevant single-nucleotide polymorphisms (SNPs).

Patients and Methods

In total, 190 patients with curative oncological resections of gastric and distal esophageal adenocarcinomas at Heidelberg University Hospital were eligible for this study. Outcome differences were determined for each SNP by analysis of clinical variables, survival, and mRNA expression levels.

Results

Significant survival differences were found on univariate analysis for usual prognostic variables (such as pTNM) and for six SNPs. On multivariate survival analysis, the SNPs rs12268840 (intron variant of MGMT, p = 0.045) and rs9972882 (intron variant of STARD3 and eQTL of PGAP3, p = 0.030) were independent and significant survival predictors along with R status and pT/pN category. Group TT of rs12268840 had the highest rate of second primary carcinoma (30.4%, p = 0.0003), lowest expression of MGMT based on cis-eQTL analysis in normal gastroesophageal tissue (p = 1.99 × 10−17), and worst oncologic outcome. Group AA of rs9972882 had the highest rate of distant metastases pM1 (42.9%, p = 0.0117), highest expression of PGAP3 (p = 1.29 × 10−15), and worst oncologic outcome.

Conclusions

Two intron variant SNPs of MGMT and STARD3 were identified that were significant survival predictors and may influence tumor biology. The data indicate that DNA methylation (MGMT) and malfunction of GPI anchoring (PGAP3) are distinct mechanisms that are relevant for tumor progression and relapse.
Synthesis of Difluoroalkenes from Thiocarbonyl Compounds via Difluorothiiranes: Electrophilic Counterpart to Wittig-Type Difluoromethylidenation
Authors: Fuchibe Kohei , Yamada Atsushi , Hachinohe Kosei , Matsumoto Kana , Takayama Ryo , Ichikawa Junji
Published: September 2021

The synthesis of 1,1-difluoro-1-alkenes was achieved by the treatment of dithioesters and thioketones with trimethylsilyl 2-fluorosulfonyl-2,2-difluoroacetate in the presence of a proton sponge catalyst, namely, 1,8-bis(dimethylamino)naphthalene. The generated electrophilic difluorocarbene (:CF2) reacted with the thiocarbonyl functionalities to form 2,2-difluorothiirane intermediates, desulfurization of which afforded the products in a Barton–Kellogg-type difluoromethylidenation. The reaction described herein is an electrophilic counterpart to the Wittig-type (nucleophilic) difluoroalkene synthesis starting from carbonyl compounds. The electrophilic difluoromethylidenation facilitated the synthesis of sulfanylated and diarylated 1,1-difluoroalkenes, including sterically hindered ones, which are inaccessible by nucleophilic difluoromethylidenation.
T1TAdb: the database of type I toxin–antitoxin systems
Authors: Tourasse Nicolas J. , Darfeuille Fabien
Published: September 2021

Type I toxin–antitoxin (T1TA) systems constitute a large class of genetic modules with antisense RNA (asRNA)-mediated regulation of gene expression. They are widespread in bacteria and consist of an mRNA coding for a toxic protein and a noncoding asRNA that acts as an antitoxin preventing the synthesis of the toxin by directly base-pairing to its cognate mRNA. The co- and post-transcriptional regulation of T1TA systems is intimately linked to RNA sequence and structure, therefore it is essential to have an accurate annotation of the mRNA and asRNA molecules to understand this regulation. However, most T1TA systems have been identified by means of bioinformatic analyses solely based on the toxin protein sequences, and there is no central repository of information on their specific RNA features. Here we present the first database dedicated to type I TA systems, named T1TAdb. It is an open-access web database (https://d-lab.arna.cnrs.fr/t1tadb) with a collection of ∼1900 loci in ∼500 bacterial strains in which a toxin-coding sequence has been previously identified. RNA molecules were annotated with a bioinformatic procedure based on key determinants of the mRNA structure and the genetic organization of the T1TA loci. Besides RNA and protein secondary structure predictions, T1TAdb also identifies promoter, ribosome-binding, and mRNA-asRNA interaction sites. It also includes tools for comparative analysis, such as sequence similarity search and computation of structural multiple alignments, which are annotated with covariation information. To our knowledge, T1TAdb represents the largest collection of features, sequences, and structural annotations on this class of genetic modules.
Os três passos do controle do erro administrativo: as diferentes etapas e objetivos na construção de parâmetros de controle
Authors: Binenbojm Gustavo , De Hollanda Dionisio Pedro
Published: September 2021

O presente artigo pretende, inicialmente, descrever as principais questões que desafiam os órgãos de controle na análise do erro administrativo. O trabalho divide o controle do erro da administração pública em três sucessivos passos: identificação do equívoco, análise da desconstituição dos efeitos da atuação administrativa e avaliação da responsabilidade pessoal dos agentes públicos envolvidos. Em sua segunda parte, o artigo trata dos principais objetivos que devem orientar a construção dosparâmetros do controle do erro. Os critérios buscam atingir finalidades parcialmente diversas, o que determina uma relativa independência entre as questões a serem enfrentadas nos três passos do controle do erro.
Discriminação racial: um legado da escravidão?
Authors: Masseko Felizardo Gabriel
Published: September 2021

A escravidão é um dos fenómenos que induziu a discriminação racial aos negros. Durante a escravidão o negro era propriedade de outra pessoa e ocupava a mais baixa posição social. Aliás, mesmo com o fim da escravidão, a discriminação racial aos negros não desapareceu. Através da pesquisa bibliográfica e pela observação dos fatos no dia-a-dia foi possível constatar esta tendência. Assim, o artigo tem como objetivo, analisar em que medida a escravidão influenciou a discriminação racial. Com vista a combater a discriminação racial, vários ativistas e organizações internacionais têm empreendido esforços no sentido de inverter o panorama, porém os desafios são maiores.
As relações Executivo- Legislativo na Primeira República: uma análise das mensagens presidenciais ao Congresso (1910-1920)
Authors: Lamarca Felipe Marques Esteves
Published: September 2021

A literatura clássica sobre a Primeira República assume que, a partir da instituição dapolítica dos governadores, o Legislativo se tornou mera instituição figurativa. Opresidente da República, em tese, negociava diretamente com os governadores dosestados para que estes evitassem que as oposições se elegessem ao CongressoNacional, tornando raros os conflitos entre os poderes. Literatura mais recente, porém,relativizou o alcance dos acordos oligárquicos. No objetivo de resgatar acomplexidade das relações entre os poderes na época, este artigo apresenta osresultados da análise das mensagens presidenciais encaminhadas pelos presidentesda República ao Congresso entre 1910 e 1920. Os dados levantados sinalizam paraconflitos entre os dois poderes, algo impensável à abordagem clássica.
O que o rap tem a dizer sobre o extermínio da juventude negra, pobre e periférica?
Authors: Arruda Daniel Péricles
Published: September 2021

O objetivo é identificar e refletir sobre o que a música rap tem a dizer a respeito do extermínio da juventude negra, pobre e periférica no Brasil, a partir da análise das canções do grupo Racionais MC’s. Essas músicas apresentam elementos afetivos, reflexivos e políticos sobre o tema. Anualmente, os homicídios de jovens, no país, conforme dados estatísticos, apresentam índices superiores aos de países em condição de “guerra declarada”. No caso brasileiro, essa situação pode ser mais complexa, pois o extermínio – em suas várias formas e seus diversos motivos – expressa-se na vida cotidiana como prática cultural, por isso é naturalizado, consentido e desejado por parte significativa da sociedade.
Entrevista de Marieta de Moraes
Authors: Reis Pompeu de Moraes Felipe
Published: September 2021

Marieta de Moraes possui doutorado em História pela UFF (1991), pós-doutorado pela École des Hautes en Sciences Sociales (1997) e pós-doutorado pela USP (2011). Coordenadora Nacional do Mestrado Profissional em Ensino de História (2013-2017); Professora Emérita do Instituto de História da UFRJ; Coordenadora do Programa de História Oral do CPDOC (1992-1995); Editora da Revista Brasileira de História (2009-2013); Presidente da Associação brasileira de História Oral (1992-1994); Presidente da International Oral History Association(IOHA) e diretora do CPDOC (1999-2005); Pesquisadora e professora titular do CPDOC/FGV (1978/2012) e editora da Revista Estudos Históricos (1992/1998). Atualmente é coordenadora do programa FGV Ensino Médio; Diretora executiva da Editora FGV; Coordenadora do Projeto binacional e interdisciplinar "Capital cities: from nation to globalization" (2015/2016”) que contou com a participação de pesquisadores brasileiros e franceses (operação bilateral FAPERJ/Sorbonne). Tem experiência na área de História, com ênfase em História do Brasil República, atuando principalmente nas seguintes áreas: historiografia, história oral, históriapolítica, história do Rio de Janeiro.
A dimensão política das identidades: modernidade e a população negra no Rio de Janeiro do século XIX
Authors: Campos da Silva Thiago
Published: September 2021

A questão geradora deste artigo é a reflexão sobre a dimensão política dasidentidades. Nesse sentido, o objetivo do trabalho é identificar se as práticas culturaisda população negra na cidade do Rio de Janeiro durante o século XIX se configuravamcomo formas de ação política. Como recurso metodológico, combino debates sobre otema das identidades afro-diaspóricas com o estudo de um contexto particular, asaber: as experiências e práticas organizativas de escravizados, libertos e livres nacidade carioca no período anterior à Abolição. Dentro desse recorte cronológico eespacial, indago se as práticas culturais e as redes de sociabilidade são formas deação política.
Reescrita do passado e conhecimento histórico na ficção contemporânea 'A historiadora obstinada', de Chimamanda Ngozi Adichie
Authors: Sampaio Costa Souza Lucas
Published: September 2021

Neste artigo, visamos, primeiro, apresentar uma perspectiva teórico-metodológica dediálogo entre Teoria da História, Literatura e Teoria Pós-colonial. Em seguida,analisamos como a ficção “A historiadora obstinada”, de autoria de ChimamandaNgozi Adichie, se apropria do passado e produz um conhecimento histórico.Considerando a mútua interrogação entre ficção e história, procuramos investigartanto os desafios quanto os empréstimos que existem entre a ficção histórica deAdichie e a historiografia. Neste sentido, sugerimos que o conto “A historiadoraobstinada” (2017) nos coloca em contato com o aspecto imprevisível da História edesafia a narrativa cristalizada pelo colonialismo ao reescrever o encontro colonial.
A formação da rede agroecológica latinoamericana em resistência às políticas públicas da revolução verde e a experiência local no Rio de Janeiro
Authors: Moreira Paula Fortini
Published: September 2021

Neste trabalho, inserido no campo da História Ambiental, pretendemos abordar aformação da rede agroecológica na América Latina, de forma geral, e afunilarmosessa trajetória, especificamente, para a nascimento da agroecologia na cidade do Riode Janeiro na década de 1980. É preciso saber que o movimento agroecológico seestabeleceu em contraposição às políticas agrícolas na qual, hoje, desencadeou noque conhecemos como agronegócio. Para isso, é necessário compreendermos adimensão das políticas públicas de expansão da agricultura industrial pela AméricaLatina e suas consequências socioambientais.
Lower mortality rate in health workers and their families infected with COVID-19 associated pneumonia in Quetta, Baluchistan
Authors: Aslam Momina , Zehri Muhammad Tahir , Mandoklel HabibUllah , Kamal Rehana , Din Mohammad
Published: September 2021

Objectives: A bunch of pneumonia cases in Wuhan, China, was caused by a novel beta-corona virus, (COVID-19) in December 2019 from where it spread rapidly across the globe. The aim of the study was to find out relevant reasons and offered suggestions to reduce the risk of infection and check clinical outcomes of the infected healthcare workers.

Methods: This study was conducted in COVID-19 Real Time Polymerase Chain Reaction (RT-PCR) laboratory, Bolan Medical Complex Hospital Quetta, Baluchistan from May to June 2020. Eight hundred (n=800) health workers and their families were included in this study. Data were obtained with standardized data collection forms shared by the WHO. Nasopharyngeal samples were collected following the WHO protocols. RNA was extracted and amplified using real time reverse transcriptase polymerase chain reaction (RT-PCR). Serum ferritin level, C-reactive protein, D-dimer and radiological results of the RT-PCR confirmed individuals were also recorded and analyzed.

Results: Among (n=800) health workers and their families 457 (57.1%) were COVID-19 PCR negative, 332 (41.5%) positive and 11 (1.4%) individuals were PCR positive but asymptomatic carriers, 234 (29.5%) were male and 103 (12.9%) were female. Mortality rate in our study was very low, only three patients (0.87%) died of this COVID-19 pneumonia.

Conclusion: Our results showed increased rate of positive cases with fortunately lower mortality rate, although this novel pneumonia was associated with acute respiratory distress syndrome ARDS and intensive care unit (ICU) admission. Timely decisions, risk awareness knowledge and supply of necessary equipments are inevitable for the control of such epidemics.

doi: https://doi.org/10.12669/pjms.37.7.4060

How to cite this:Aslam M, Zehri MT, Mandoklel H, Kamal R, Din M. Lower mortality rate in health workers and their families infected with COVID-19 associated pneumonia in Quetta, Baluchistan. Pak J Med Sci. 2021;37(7):---------.  doi: https://doi.org/10.12669/pjms.37.7.4060

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Donor Chimerism Study by Single Nucleotide Polymorphism using SYBR green based Real Time PCR
Authors: Nayyar Ayesha , Ahmed Suhaib
Published: September 2021

Objective: To optimize and evaluate a real time PCR of Single Nucleotide Polymorphism by SYBR Green method for detection of donor chimerism after haematopoietic stem cell transplantation.

Methods: This descriptive study was conducted at Genetic Resource Centre (GRC) Lab Rawalpindi from Oct 2017 - Dec 2019. A total of twenty patients of post haematopoietic stem cell transplant with various haematological disorders were studied to see the status of donor chimerism by using SNP real time PCR using SYBR Green method and short tandem repeat PCR. These patients had undergone allogeneic HSCT from HLA-matched sibling donors at Pakistan Institute of Medical Science and Armed Forces Bone Marrow Transplant Centre.

Results: Real time PCR using SYBR Green was able to detect significant amount of chimerism in all 20 patients having undergone HSCT. Regarding precision of the real time PCR assay the mean value of donor chimerism was 94.1% (SD 3.96) and by STR PCR it was 95.1% (SD 1.41). The assay was found to be sensitive with a detection limit of <1%.

Conclusion: Our results demonstrate that SNP analysis by SYBR Green real time PCR may be used for the evaluation of chimerism status in patients having undergone HSCT with a sensitivity of <1%. Hence donor chimerism by this sensitive method can be used in monitoring of chimerism in post-transplant patients with various haematological disorders.

doi: https://doi.org/10.12669/pjms.37.7.4203

How to cite this:Nayyar A, Ahmed S. Donor Chimerism Study by Single Nucleotide Polymorphism using SYBR green based Real Time PCR. Pak J Med Sci. 2021;37(7):---------. doi: https://doi.org/10.12669/pjms.37.7.4203

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Μοντελοποίηση υπηρεσίας τηλεϊατρικής για την εξ αποστάσεως διάγνωση και αξιολόγηση συναισθηματικών διαταραχών
Authors: Κωνσταντοπούλου Γεωργία
Published: September 2021

Τα τελευταία χρόνια, υπάρχει μεγάλη πρόοδος όσον αφορά τόσο τη διάγνωση και τα κλινικά χαρακτηριστικά των ψυχιατρικών ασθενειών, όσο και τους παράγοντες κινδύνου, τα αίτια και την παθοφυσιολογία τους. Μια βασική κατηγορία Ψυχικών Διαταραχών είναι οι Συναισθηματικές Διαταραχές ή Διαταραχές Διάθεσης, οι οποίες χαρακτηρίζονται από διαταραχή της συναισθηματικής διάθεσης. Περισσότερο από το 14% του πληθυσμού έχει διαταραχή της διάθεσης και περισσότερο από 50% δεν λαμβάνει θεραπεία. Σε απάντηση ενός πλήθους προκλήσεων της παροχής ιατρικής φροντίδας σε ασθενείς που πάσχουν από τις διαταραχές αυτές, οι Τεχνολογίες της Πληροφορίας και των Επικοινωνιών (ΤΠΕ) μπορούν να δώσουν νέες προοπτικές και σημαντικές δυνατότητες βελτίωσης στην περίθαλψη της υγείας. Η αξιοποίηση σύγχρονων τεχνολογικών λύσεων διευκολύνει μεταξύ άλλων την απομακρυσμένη διάγνωση, τη διαρκή παρακολούθηση, την έγκαιρη διαχείριση εκτάκτων περιστατικών και την άμεση και εύκολη επικοινωνία μεταξύ ιατρών και ασθενών. Ειδικότερα, η αξιοπιστία των εξ’ αποστάσεως διαγνώσεων μέσω τηλεψυχιατρικής έχει τύχει εκτενούς διερεύνησης και έχει βρεθεί ότι σχετίζεται σημαντικά με την ποιότητα της χρησιμοποιούμενης τεχνολογίας, με την πλειοψηφία των ερευνών να υποστηρίζει ότι οι διαγνώσεις μέσω τηλεψυχιατρικής δεν στερούνται αξιοπιστίας συγκριτικά με δια ζώσης αξιολογήσεις. Σε αυτό το πλαίσιο, στόχος της παρούσας εργασίας είναι η ανάπτυξη, η χρήση και η αξιολόγηση μίας διαδικτυακής εφαρμογής που θα επιτρέπει μία αρχική εξ’ αποστάσεως αξιολόγηση της κατάστασης της υγείας ατόμων που αισθάνονται δυσφορία λόγω άγχους, ή συμπτωμάτων κατάθλιψης. Η εφαρμογή αυτή χορηγεί βηματικά τις κλίμακες HADS, STAI, BECK και RASS και βάσει των απαντήσεών τους, οι χρήστες ενημερώνονται για την κατάσταση της ψυχικής τους υγείας και ενθαρρύνονται να επισκεφθούν κάποιο ειδικό εφόσον κριθεί απαραίτητο.