Miracle-dz/UniFAR-FTUs huggingface dataset:
KPC-Mediated Resistance to Ceftazidime-Avibactam and Collateral Effects in Klebsiella pneumoniae

Carbapenem-resistant Enterobacterales, such as Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae, represent a major threat to public health due to their rapid spread. Novel drug combinations such as ceftazidime-avibactam (CZA), combining a broad-spectrum cephalosporin along with a broad-spectrum β-lactamase inhibitor, have recently been introduced and have been shown to exhibit excellent activity toward multidrug-resistant KPC-producing Enterobacterales strains. ABSTRACT Carbapenem-resistant Enterobacterales, such as Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae, represent a major threat to public health due to their rapid spread. Novel drug combinations such as ceftazidime-avibactam (CZA), combining a broad-spectrum cephalosporin along with a broad-spectrum β-lactamase inhibitor, have recently been introduced and have been shown to exhibit excellent activity toward multidrug-resistant KPC-producing Enterobacterales strains. However, CZA-resistant K. pneumoniae isolates are now being increasingly reported, mostly corresponding to producers of KPC variants. In this study, we evaluated in vitro the nature of the mutations in the KPC-2 and KPC-3 β-lactamase sequences (the most frequent KPC-type enzymes) that lead to CZA resistance and the subsequent effects of these mutations on susceptibility to other β-lactam antibiotics. Single-step in vitro selection assays were conducted, resulting in the identification of a series of mutations in the KPC sequence which conferred the ability of those mutated enzymes to confer resistance to CZA. Hence, 16 KPC-2 variants and 10 KPC-3 variants were obtained. Production of the KPC variants in an Escherichia coli recombinant strain resulted in a concomitant increased susceptibility to broad-spectrum cephalosporins and carbapenems, with the exceptions of ceftazidime and piperacillin-tazobactam, compared to wild-type KPC enzymes. Enzymatic assays showed that all of the KPC variants identified exhibited an increased affinity toward ceftazidime and a slightly decreased sensitivity to avibactam, sustaining their impact on CZA resistance. However, their respective carbapenemase activities were concurrently negatively impacted.
Intrinsic ferroelectricity and large bulk photovoltaic effect in novel two-dimensional buckled honeycomb-like lattice of NbP: first-principles study

Using first-principles calculations, we predict that the two-dimensional (2D) monolayers of NbP with the buckled honeycomb-like and puckered tetragonal structure can be obtained from the (110) and (001) orientations, respectively, of its bulk crystal structure. The electronic properties of these monolayers are spectacularly different as tetragonal lattice is metallic whereas the honeycomb-like lattice (h-NbP) is a semiconductor and exhibits intrinsic ferroelectricity originating from a rare sd 2–sp 2 hybridization. The shift current bulk photovoltaic effect (BPVE) is systematically investigated in the h-NbP monolayer (1.21 Å thickness) using the Wannier interpolation method. Strong absorption of visible light at ∼2 eV and a large 3D shift current of ∼180 μA V−2 is obtained which is attributed to the partial delocalization of Bloch states due to sd 2–sp 2 hybridization. We compare the shift current response of h-NbP monolayer with that of some previously reported bulk ferroelectrics and 2D monolayers, suggesting that h-NbP monolayer can yield a large shift current at an ultimate thickness and is a promising 2D material for the BPVE application under the visible light. Strain effect is also investigated, revealing that the h-NbP monolayer is dynamically stable up to a strain limit of ±3%, and the shift current increases by ∼9% at a compressive strain of −3% as the Bloch states are more delocalized due to the strengthening of sd 2–sp 2 hybridization. The results presented in this study can pave the paths to fabricate the 2D monolayered structures of NbP, and realize the BPVE based next-generation solar cells of h-NbP monolayer.
Mammalian tracheal development and reconstruction: insights from in vivo and in vitro studies

ABSTRACT The trachea delivers inhaled air into the lungs for gas exchange. Anomalies in tracheal development can result in life-threatening malformations, such as tracheoesophageal fistula and tracheomalacia. Given the limitations of current therapeutic approaches, development of technologies for the reconstitution of a three-dimensional trachea from stem cells is urgently required. Recently, single-cell sequencing technologies and quantitative analyses from cell to tissue scale have been employed to decipher the cellular basis of tracheal morphogenesis. In this Review, recent advances in mammalian tracheal development and the generation of tracheal tissues from pluripotent stem cells are summarized.
Systematic Review of Quality Improvement Projects Related to Intershift Nursing Handover

Supplemental Digital Content is Available in the Text. Background: Nursing handover is a real-time process in which patient-specific information is passed between nurses to ensure the continuity and safety of patient care. Purpose: The purpose of this study was to determine the effects of quality improvement (QI) projects in improving the intershift nursing handover process. Methods: A computerized search was performed of electronic databases for articles published during 2009-2019 in English or Korean for which the full texts were available. The included studies involved QI projects, handover between nurses, and intershift handover. The QI-MQCS (Quality Improvement Minimum Quality Criteria Set) was used to appraise the quality of QI strategies. Results: The handover methods used in the 22 QI projects could be broadly divided into 2 types: (1) using a standardized communication tool; and (2) involving patient-participation bedside handover. Conclusions: The published research on intershift handover-related QI projects employed standardized communication tools and the patient-participation bedside handover method to reduce adverse events and handover times and increase the satisfaction of patients and nurses. Future studies should measure the changes in patient safety-related outcomes.
Risk of hypertension with anti-VEGF monoclonal antibodies in cancer patients: a systematic review and meta-analysis of 105 phase II/III randomized controlled trials

Abstract We performed a meta-analysis to fully investigate the hypertension of anti-VEGF mAbs in cancer patients. Databases were searched for randomized controlled trials (RCTs) treated with anti-VEGF mAbs till January 2021. The relevant RCTs in cancer patients treated with anti-VEGF mAbs were retrieved and the systematic evaluation was conducted. One hundred and five RCTs and 65358 patients were included. Our study suggests that anti-VEGF mAbs significantly increased the risks of all-grade (RR, 3.22; 95%CI, 2.83-3.65; p < 0.00001; I2=71%) and high-grade (RR, 6.15; 95%CI, 5.58-6.78; p < 0.00001; I2=48%) hypertension in cancer patients. Those risks may be dependent on drug type. Icrucumab did not association with an increased risk of hypertension. The RR of hypertension did not vary significantly according to the type of cancer, line of therapy, and treatment duration. The available data suggested that the use of anti-VEGF mAbs were associated with a significantly increased risk of hypertension.
Braf mutation induces rapid neoplastic transformation in the aged and aberrantly methylated intestinal epithelium

Objective Sessile serrated lesions (SSLs) are common across the age spectrum, but the BRAF mutant cancers arising occur predominantly in the elderly. Aberrant DNA methylation is uncommon in SSL from young patients. Here, we interrogate the role of ageing and DNA methylation in SSL initiation and progression. Design We used an inducible model of Braf mutation to direct recombination of the oncogenic Braf V637E allele to the murine intestine. BRAF mutation was activated after periods of ageing, and tissue was assessed for histological, DNA methylation and gene expression changes thereafter. We also investigated DNA methylation alterations in human SSLs. Results Inducing Braf mutation in aged mice was associated with a 10-fold relative risk of serrated lesions compared with young mice. There were extensive differences in age-associated DNA methylation between animals induced at 9 months versus wean, with relatively little differential Braf-specific methylation. DNA methylation at WNT pathway genes scales with age and Braf mutation accelerated age-associated DNA methylation. In human SSLs, increased epigenetic age was associated with high-risk serrated colorectal neoplasia. Conclusions SSLs arising in the aged intestine are at a significantly higher risk of spontaneous neoplastic progression. These findings provide support for a new conceptual model for serrated colorectal carcinogenesis, whereby risk of Braf-induced neoplastic transformation is dependent on age and may be related to age-associated molecular alterations that accumulate in the ageing intestine, including DNA methylation. This may have implications for surveillance and chemopreventive strategies targeting the epigenome.
An alternative method for radioactivity measurement in quantitative bone SPECT/CT imaging

Bone scintigraphy with combined single-photon emission computed tomography (SPECT) and computed tomography (CT) has become widely used for the detection of bone metastases. However, calculation of the semi-quantitative standardized uptake value (SUV) requires measurement of the pre- and post-injection radioactivity of the radiopharmaceutical. This study aimed to compare measured and fixed input radioactivity values for quantitative SPECT/CT bone imaging to examine whether the fixed measurement method of radiopharmaceutical radioactivity could be used as an alternative method. Four different methods were used to quantify the Tc-99m hydroxymethylene diphosphonate input radioactivity: (A) measured pre- and post-injection radioactivity values; (B) measured pre-injection and fixed post-injection radioactivity values; (C) fixed pre-injection and measured post-injection radioactivity values; (D) fixed pre- and post-injection radioactivity values. All SPECT/CT acquisitions were analyzed using bone SPECT analysis software, and the semi-quantitative parameters (SUVpeak and SUVmean) were recorded and compared for each analytical method. Two semi-quantitative parameters showed significant differences between analytical methods A and B, A and D, and C and D. However, an additional subgroup analysis performed on patients whose median post-injection measured radioactivity value was <1.5 MBq showed no significant differences in parameters between all analytical methods. Measurement of the radiopharmaceutical radioactivity can be an alternative method because it reduces the volume of radioactivity post-injection. The simplified fixed measurement method of radiopharmaceutical radioactivity can be used as an alternative method in cases when measuring the radioactivity in quantitative bone SPECT/CT imaging is missed.
Post-operative serum procalcitonin vs C reactive Protein as a marker of post-operative infectious complications in pancreatic surgery. A systemic review and metaanalysis.

Aim of Study: Aim of this meta-analysis was to compare diagnostic accuracy of C reactive Protein and Procalcitonin between postoperative day 3 to 5 in predicting infectious complications post pancreatic surgery. Methods: Systemic literature search was performed using MEDLINE, EMBASE and SCOPUS to identify studies evaluating the diagnostic accuracy of Procalcitonin (PCT) and C-Reactive Protein (CRP) as a predictor for detecting infectious complications between postoperative days (POD) 3 to 5 following pancreatic surgery. A meta-analysis was performed using random effect model and pooled predictive parameters. Geometric means were calculated for PCT cut offs. The work has been reported in line with PRISMA guidelines. Results: After applying inclusion and exclusion criteria 15 studies consisting of 2212 patients were included in the final analysis according to PRISMA guidelines. Pooled sensitivity, specificity ,Area under curve and diagnostic odds ratio (DOR)for day 3 C-reactive protein was respectively 62%,67% 0.772 and 6.54. Pooled sensitivity, specificity , Area under curve and diagnostic odds ratio (DOR)for day 3 procalcitonin was respectively 74%,79%,0.8453 and 11.03. Sensitivity, specificity, Area under curve, and Diagnostic odds ratio for day 4 C-reactive protein was respectively 60%,68%, 0.8022 and 11.90. Pooled Sensitivity, specificity and Diagnostic odds ratio of post-operative day 5 procalcitonin level in predicting infectious complications were respectively 83%,70% and 12.9. Pooled Sensitivity, specificity, AUROC and diagnostic odds ratio were respectively 50%,70%, 0.777 and 10.19. Conclusion: Post-operative procalcitonin is better marker to predict post-operative infectious complications after pancreatic surgeries and post-operative day 3 procalcitonin has highest diagnostic accuracy.
Cancer care disparities among Australian and Aotearoa New Zealand Indigenous peoples

Purpose of review Persistent and significant inequalities for Indigenous people with cancer around the globe exist, arising from colonial settlement of Indigenous land with profound social, economic and cultural impacts. We summarize recent publications concerning cancer disparities affecting Australian Aboriginal and Torres Strait Islander Peoples and Aotearoa New Zealand Māori Peoples. Recent findings Cancer-free survival and overall survival statistics testify to the urgent need to ‘close the gap’. For Indigenous peoples in Australia and New Zealand, disparity persists along the cancer care pathway, from increased risk factors to lower screening access, health resource utilization and survivorship care. Recent publications highlight multimorbidity as contributing to poor cancer outcomes in Indigenous populations. The implementation of tailored Optimal Care Pathways is described, as is the validation of tailored tools capturing the perspectives of Indigenous persons. Finally, the importance of Indigenous-led research is emphasized. Summary Cancer-specific outcomes in Indigenous people of Australia and New Zealand remain poor with many widening disparities compared to non-indigenous populations. A growing body of epidemiological, health service and clinical research is documenting both the problems and potential solutions. Further work is needed in both broad health policies and the workforce, in building cultural competence to optimize individual care encounters.
Influence of CMO pharmaceutical care model-based intervention on readmission rate in high risk HIV patients: the INFARDAR study

ABSTRACT Background Many studies have indicated that hospitalization and readmissions occur frequently, especially among people living with HIV. The aim of the study was to determine the effectiveness of a programmed and structured pharmaceutical intervention, based on “CMO PC model” to reduce the readmission rate in high-risk HIV patients. Material and methods This was a single-center, prospective study based on a structured health intervention conducted between March-2017 and March-2018 with 12 months of follow-up at outpatient pharmacy services. At discharge, HIV patients included were classified according to the risk of readmission as low or high risk patients, being the latter proposed to participate. The selected patients were randomly assigned to a control group (usual care) or intervention group (including stratification-motivational interview and new technologies: CMO pharmaceutical care). The primary endpoint was readmission rate at one year of follow-up in each group. Results A total of 39 patients were included. As regards the main variable, in the intervention group, 21,4% (n=3) of patients were readmitted in the first year after discharge vs. 66,7% (n=6) in the control group (p=0,042). Conclusions Tailored pharmaceutical care based on risk stratification, motivational interviewing, and new technologies has a positive influence to reduce the percentage of readmission in high risk HIV patients.
Optical genome mapping identifies a germline retrotransposon insertion in SMARCB1 in two siblings with atypical teratoid rhabdoid tumors

In a subset of pediatric cancers, a germline cancer predisposition is highly suspected based on clinical and pathological findings, but genetic evidence is lacking, which hampers genetic counseling and predictive testing in the families involved. We describe a family with two siblings born from healthy parents who were both neonatally diagnosed with atypical teratoid rhabdoid tumor (ATRT). This rare and aggressive pediatric tumor is associated with biallelic inactivation of SMARCB1, and in 30% of the cases, a predisposing germline mutation is involved. Whereas the tumors of both siblings showed loss of expression of SMARCB1 and acquired homozygosity of the locus, whole exome and whole genome sequencing failed to identify germline or somatic SMARCB1 pathogenic mutations. We therefore hypothesized that the insertion of a pathogenic repeat‐rich structure might hamper its detection, and we performed optical genome mapping (OGM) as an alternative strategy to identify structural variation in this locus. Using this approach, an insertion of ~2.8 kb within intron 2 of SMARCB1 was detected. Long‐range PCR covering this region remained unsuccessful, but PacBio HiFi genome sequencing identified this insertion to be a SINE‐VNTR‐Alu, subfamily E (SVA‐E) retrotransposon element, which was present in a mosaic state in the mother. This SVA‐E insertion disrupts correct splicing of the gene, resulting in loss of a functional allele. This case demonstrates the power of OGM and long‐read sequencing to identify genomic variations in high‐risk cancer‐predisposing genes that are refractory to detection with standard techniques, thereby completing the clinical and molecular diagnosis of such complex cases and greatly improving counseling and surveillance of the families involved. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Electrostatic Interactions Explain the Higher Binding Affinity of the CR3022 Antibody for SARS-CoV-2 than the 4A8 Antibody

A structural understanding of the mechanism by which antibodies bind SARS-CoV-2 at the atomic level is highly desirable as it can tell the development of more effective antibodies to treat Covid-19. Here, we use steered molecular dynamics (SMD) and coarse-grained simulations to estimate the binding affinity of the monoclonal antibodies CR3022 and 4A8 to the SARS-CoV-2 receptor-binding domain (RBD) and SARS-CoV-2 N-terminal domain (NTD). Consistent with experiments, our SMD and coarse-grained simulations both indicate that CR3022 has a higher affinity for SARS-CoV-2 RBD than 4A8 for the NTD, and the coarse-grained simulations indicate the former binds three times stronger to its respective epitope. This finding shows that CR3022 is a candidate for Covid-19 therapy and is likely a better choice than 4A8. Energetic decomposition of the interaction energies between these two complexes reveals that electrostatic interactions explain the difference in the observed binding affinity between the two complexes. This result could lead to a new approach for developing anti-Covid-19 antibodies in which good candidates must contain charged amino acids in the area of contact with the virus.
The Role of Discrimination Experiences in Postrape Adjustment Among Racial and Ethnic Minority Women

Although recent studies have linked discrimination frequency among Black and Latinx individuals to PTSD symptom severity, to our knowledge, these associations have yet to be examined among a diverse sample of recent rape survivors. The current secondary analysis of existing data examined the role of discrimination experiences in post-traumatic stress disorder (PTSD) symptoms, depression, and alcohol and drug problems among a racially and ethnically diverse sample of recent rape survivors. Participants were 139 Black (48.2%; n = 67), American Indian (18.7%; n = 26), Hispanic (15.1%; n = 21), and mixed race (17.3%; n = 24) girls and women age 15 or older who presented to the emergency department (ED) for a sexual assault forensic medical exam. They were randomly assigned to one of three intervention conditions, and completed a six-month postrape follow-up, including questions about mental health, substance use problems, and discrimination experiences. Regression analyses revealed that Black women experienced discrimination in significantly more situations and with greater frequency compared to American Indian and Hispanic women. Discrimination frequency was positively associated with PTSD and depression symptoms even after controlling for age, education, race, and intervention condition, but was not associated with alcohol or drug problems. Findings highlight the importance of attending to the heterogeneous experiences of discrimination among racial and ethnic minority women. Future work should adapt evidence-based early interventions to be maximally effective at combating both racial and sexual trauma exposures.
A Multiperiod Model for Assessing the Socioeconomic Impacts of Oil Spills during Arctic Shipping

As the rate of ice melt in the Arctic increases, the potential for shipping activities is also increasing. However, infrastructure along the northwest passage (NWP) in Canada's Arctic is almost nonexistent. This presents major challenges to any response efforts in the case of a natural disaster. Also, the Arctic is home to many indigenous communities, as well as flora and fauna. Thus, it is of vital importance to protect the livelihood of the rights holders in this area and the Arctic marine environment. To do this, it is necessary to develop a decision‐making tool to assess the potential risk of pollutants arising from increased shipping activity. Understanding such, this article assesses the impacts of a potential oil spill on communities in the Canadian Arctic. The consequences of risk are presented using a multiperiod model while the likelihood is analyzed using Bayesian Network. The output of the multiperiod model is incorporated into an influence diagram for risk assessment purposes. The Bayesian model benefits from expert elicitation from the crew aboard a research ship passing through the NWP. Information was also obtained from marine insurance companies, government representatives, and other Arctic specialized professionals. The risk‐based model is subsequently applied to the Canadian Arctic area, with the aim of evaluating the impact of a potential oil spill through shipping.
Physical exercise increases global and gene‐specific (interleukin‐17 and interferon‐γ) DNA methylation in lymphocytes from aged women

What is the central question of this study? Is lymphocyte DNA methylation differentially modulated by resistance training and aerobic exercise in older women? What is the main finding and its importance? The practice of resistance training led to an increased global DNA methylation in lymphocytes. The exercise‐induced increase of inflammatory genes methylation may be associated with immune function impairment during ageing.