bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal personalized urinary tumor DNA analysis in muscle-invasive bladder cancer from the neoadjuvant immunotherapy trial RJBLC-I2N003.
Authors: Zhang Ruiyun , Zang Jingyu , Xie Feng , Zhang Yue , Shahatiaili Akezhouli , Wang Yiqiu , Du Pan , Jia Shidong , Zhuang Guanglei , Huang Yiran , Chen Haige
Published: February 2022

552

Background: RJBLC-I2N003 is an investigator-initiated study to evaluate the clinical activity and predictive biomarkers for neoadjuvant immunotherapy with toripalimab (anti-PD-1) in muscle invasive bladder cancer (MIBC). Methods: Twenty patients with pathologically confirmed MIBC were enrolled and received toripalimab (3 mg/kg Q2W, 4 cycles) before radical cystectomy. The safety and efficacy of neoadjuvant toripalimab were assessed. Serial urinary cell-free DNA (ucfDNA) and blood cell-free DNA (bcfDNA) were obtained at baseline and after each cycle of toripalimab treatment. Personalized minimal residual disease (MRD) assays and low-pass whole genome sequencing (LP-WGS) were applied to analyze liquid biopsy samples. Results: Eighteen patients (90%) completed all 4 cycles of neoadjuvant treatment. Grade 3-4 immune-related adverse events occurred in two patients (10%). Eight patients (40%) achieved a pathological complete response (pCR). Thirteen patients (65%) had no remaining invasive disease (pCR or pTisN0/pTaN0). Pre-treatment somatic variants and copy number abnormalities were prevalently detected in ucfDNA as compared to bcfDNA. On-treatment urinary tumor DNA (utDNA) clearance was associated with objective responses. Preliminary concordance was observed between molecular and pathological MRD status. Conclusions: These findings suggest that neoadjuvant administration of PD-1 blockade followed by surgical resection represents a feasible and efficacious approach to treat MIBC. The exploratory biomarker assessment demonstrates the potential utility of longitudinal personalized utDNA analysis to complement existing trial endpoints.
Phase 1 study of JNJ-69086420, an actinium-225-labeled antibody targeting human kallikrein-2, for advanced prostate cancer.
Authors: Morris Michael J. , Sartor A. Oliver , Wong Jeffrey Y.C. , Max Steven I , Xie Hong , Russell Mike , Divgi Chaitanya R , Patricia Daniel , Avadhani Anjali Narayan , Nordquist Luke T.
Published: February 2022

TPS206

Background: Radioligand therapy for metastatic castration resistant prostate cancer (mCRPC) has been shown to prolong survival, delay disease progression, and improve quality of life, raising hopes that these gains will be amplified with even more cancer-specific targets and more powerful radioligands. Human kallikrein-related peptidase 2 (hK2) is a tumor-associated member of the kallikrein family that shares significant homology to prostate-specific antigen and is minimally expressed in normal non-prostate tissues. JNJ-69086420 (JNJ-420; 225Ac-DOTA-h11B6 [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]), is a first-in-class radioimmunotherapy targeted to hK2 antigen. In a phase 0 study of [111In]-DOTA-h11B6, patients (pts) with mCRPC (progressed on standard therapies), treatment with a single dose of [111In]-DOTA-h11B6 (2 mg) with/without 8 mg h11B6, demonstrated safety, good tumor localization, nominal normal-organ uptake, and no difference in PK between 2 and 10 mg antibody mass (Morris et al. J Clin Oncol. 2021 39:6 suppl, 122). We have initiated the first-in-human study to assess the safety, pharmacokinetics (PK), pharmacodynamic (PD), and clinical activity of Ac-225 radiolabeled JNJ-420, to determine its recommended phase 2 dose (RP2D) in adults with advanced PC. Methods: This open-label, multicenter, phase 1 study will recruit approximately 50 men (aged ≥18 years) with advanced PC across dose escalation (Part 1) and expansion (Part 2) parts. Key eligibility criteria: mCRPC with histologic confirmation of adenocarcinoma, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, adequate organ function based on hematology and serum chemistry, and 1 or more prior novel androgen receptor-targeted therapies (prior chemotherapy acceptable). Key exclusion criteria: prior treatment with radium/strontium/samarium/radioconjugate therapy, superscan findings as protocol defined, active central nervous system metastases. In Part 1, men will receive intravenous (IV) injection of 50 μCi/ 2 mg JNJ-420 (once every 8 weeks) with one or multiple doses; escalation of dose levels to be based on dose limiting toxicities (DLTs) evaluation, until RP2D identification. In Part 2, JNJ-420 is to be given at one of the RP2D(s) determined in Part 1. Primary endpoint is safety (incidence and severity [grading per NCI-CTCAE V5.0] of AEs including DLTs). Secondary endpoints include prostate specific antigen response rate, overall response rate (PCWG3 modified RECIST 1.1 criteria), PK, PD, immunogenicity, and biomarker analyses. Enrollment began in Dec 2020; as of Sep 2021, 4 sites have been initiated and 14 pts enrolled; currently, dose escalation is ongoing. Clinical trial information: NCT04644770.
ORCHID: A phase II study of olaparib in metastatic renal cell carcinoma patients harboring a BAP1 or other DNA repair gene mutations.
Authors: Ged Yasser , Rifkind Irina , Michalik Amber , Carducci Michael Anthony , Markowski Mark Christopher
Published: February 2022

TPS400

Background: Metastatic renal cell carcinoma (RCC) comprises a wide set of heterogenous tumors, many of which are increasingly recognized with alterations that affect genomic instability. Several studies demonstrated that DNA repair pathways are frequently disrupted in RCC. Recent In vitro studies have shown that RCC cells are sensitive to PARP inhibitors, with subsequent increased DNA replication stress, DNA synthesis suppression and eventual increased cell cycle arrest. In addition, other studies demonstrated reduced repair of double stranded DNA (dsDNA) breaks following conditional knockout of BAP-1 suggesting that PARP inhibitors may result in synthetic lethality in the setting of BAP-1 inactivation. In light of this we have initiated a phase 2 clinical trial to examine the activity of the PAPR inhibitor olaparib in metastatic RCC with BAP-1 and select DNA repair gene alterations. Methods: This is an open-label, single-arm, investigator-initiated phase II trial of olaparib in patients with metastatic RCC (NCT03786796). Eligibility criteria include age ≥18 years; histologically confirmed, unresectable, locally advanced or mRCC; disease progression after at least one VEGF targeted therapy or immune-checkpoint inhibitor, evidence of deleterious somatic or germline DDR gene alteration ( BAP1, ATM, BRCA1, BRCA2, PALB2, CHEK2, BRIP1, RAD51C, BARD1, CDK12, CHEK1, FANCL, PP2R2A, RAD51B, RAD51D, or RAD54L). A total of 20 patients will be enrolled with the primary endpoint of disease control rate (defined as complete response [CR], partial response [PR], or stable disease [SD]) at six months of treatment) according to RECIST version 1.1. Patients will be treated with olaparib at an initial dose of 150mg by mouth twice daily. If olaparib is tolerated without any grade > 3 adverse events after one month, the dose will be increased to the FDA-approved dose of 300mg by mouth twice daily. Patients will be followed monthly with clinic visits, safety labs, and toxicity assessments. Treatment will be continued until radiographic progression (RECIST version 1.1) or unmanageable toxicity requiring drug cessation. Secondary endpoints include progression-free survival, best overall response, and safety. The study is currently open to enrollment. Clinical trial information: NCT03786796.
Study EV-302: A two-arm, open-label, randomized controlled phase 3 study of enfortumab vedotin in combination with pembrolizumab versus chemotherapy in previously untreated advanced urothelial carcinoma (aUC) (trial in progress).
Authors: Van Der Heijden Michiel Simon , Gupta Shilpa , Galsky Matt D. , Derleth Christina Louise , Lee Sue , Kataria Ritesh S. , Powles Thomas
Published: February 2022

TPS589

Background: Platinum-based chemotherapy is standard first line (1L) therapy for aUC. Maintenance therapy may be offered for patients (pts) who do not progress on 1L chemotherapy. However, not all pts are eligible for maintenance therapy, with many succumbing to their disease prior to 2L. Therefore, there is a persistent unmet need for safe and effective drug combinations in the 1L setting. Enfortumab vedotin (EV) is a Nectin-4 directed antibody-drug conjugate (ADC) comprised of a fully human mAb conjugated to the microtubule-disrupting agent, monomethyl auristatin E (MMAE), via a protease-cleavable linker. EV has previously shown an OS benefit vs chemotherapy in pts with locally advanced or metastatic urothelial carcinoma who had previously received platinum-based therapy and a PD-(L)1 inhibitor (Powles NEJM 2021). EV is FDA-approved in this and other settings (PADCEV, Seagen Inc., 2021). Preclinical studies showed that MMAE containing ADCs, including EV, induce evidence of immunogenic cell death and can enhance anti-tumor immunity, thereby laying the foundation for EV-PD-1/PD-L1 inhibitor combination (Liu Cancer Res 2020; Cao Can Res 2016). EV-302 will evaluate the efficacy and safety of EV+pembrolizumab (EV+P) combination vs gemcitabine+cisplatin (gem+cis) or carboplatin (carbo) in pts with previously untreated aUC. Methods: EV-302/KN-A39 (NCT04223856) evaluates EV+P combination vs gem+cis or carbo in previously untreated pts with aUC. Eligibility criteria include pts with measurable disease, an ECOG status of ≤2, and eligible to receive EV, P, and cis or carbo. EV+P combination includes EV (1.25 mg/kg) administration on Days 1 and 8 with P (200 mg) on Day 1. Gem+cis or carbo includes: gem (1000 mg/m2) on Days 1 and 8; and cis (70 mg/m2) or carbo (AUC 4.5 or 5) on Day 1 of every 3-wk cycle. Randomization is 1:1 with stratification factors: cis eligibility, PD-L1 expression, and liver metastases. The primary endpoints are PFS and OS for EV+P compared to gem+cis or carbo. Other endpoints include ORR, duration of response, disease control rate, AEs, patient reported outcomes, PK, and biomarkers. The study opened March 2020 with sites actively enrolling globally. Clinical trial information: NCT04223856.
Mortality After Late Breast Cancer Recurrence in Denmark
Authors: Pedersen Rikke Nørgaard , Mellemkjær Lene , Ejlertsen Bent , Nørgaard Mette , Cronin-Fenton Deirdre P.
Published: February 2022

PURPOSE

Late breast cancer (BC) recurrence (ie, ≥ 10 years after primary diagnosis) may have a more favorable prognosis than earlier recurrence. We investigated the risk of BC death after late recurrence, identified prognostic factors, and compared survival after early and late recurrence.

METHODS

Using the Danish Breast Cancer Group and other nationwide databases, we identified women with early or late BC recurrence during 2004-2018, who were alive 6 months after recurrence. We followed them until BC death, death from other causes, emigration, 10 years, or December 31, 2018, whichever came first. We calculated mortality rates (MRs) per 1,000 person-years (PY) and cumulative BC mortality, for early versus late recurrence, and by characteristics of the primary tumor and the late recurrence. Using Cox regression, we calculated adjusted hazard ratios (HRs) for BC death, accounting for death from other causes as competing risks.

RESULTS

Among 2,004 patients with late recurrence, 721 died of BC with a median survival time of 10 years (MR = 84.8 per 1,000 PY; 10-year cumulative mortality = 50%). Among 1,528 patients with early recurrence, 1,092 BC deaths occurred with a median survival time of 4 years (MR = 173.9 per 1,000 PY; 10-year cumulative mortality = 72%). We observed a lower hazard of BC-specific death among patients who developed late compared with early recurrence (hazard ratio = 0.72; 95% CI, 0.62 to 0.85). Advanced stage at primary diagnosis, distant metastases, adjuvant treatment for locoregional recurrence, and systemic treatment for distant recurrence were associated with increased mortality after late recurrence. Breast-conserving surgery at primary diagnosis, locoregional recurrence, and surgery for recurrence were associated with lower mortality after late recurrence.

CONCLUSION

Patients with late recurrence had more favorable prognosis than patients with early recurrence. The localization of recurrent disease was the main prognostic factor for BC death.
Lost Venous Access Guidewire Identified by Its Late Cervical Protrusion: Case Report
Authors: Osailan Ahmed , De Queiroz Siqueira Mathilde , Bouvet Lionel , Chassard Dominique
Published: February 2022

We report a pediatric patient who underwent a central venous catheter (CVC) insertion and presented with a sudden protrusion of a guidewire from the neck 26 months later. The guidewire was extracted via femoral venotomy. A 5-cm portion of the guidewire adhering to the superior vena cava wall was left in place. We recommend always using a CVC checklist, inspecting the guidewire before and after insertion, and carefully examining the postinsertion radiographs. This checklist should be mandatory with every CVC insertion, including the perioperative period.
Lesbian Potentiality and Feminist Media in the 1970s
Authors: Samer Rox
Published: February 2022

In Lesbian Potentiality and Feminist Media in the 1970s, Rox Samer explores how 1970s feminists took up the figure of the lesbian in broad attempts to reimagine gender and sexuality. Samer turns to feminist film, video, and science fiction literature, offering a historiographical concept called “lesbian potentiality”—a way of thinking beyond what the lesbian was, in favor of how the lesbian signified what could have come to be. Samer shows how the labor of feminist media workers and fans put lesbian potentiality into movement. They see lesbian potentiality in feminist prison documentaries that theorize the prison industrial complex’s racialized and gendered violence and give image to Black feminist love politics and freedom dreaming. Lesbian potentiality also circulates through the alternative spaces created by feminist science fiction and fantasy fanzines like The Witch and the Chameleon and Janus. It was here that author James Tiptree, Jr./Alice B. Sheldon felt free to do gender differently and inspired many others to do so in turn. Throughout, Samer embraces the perpetual reimagination of “lesbian” and the lesbian’s former futures for the sake of continued, radical world-building.
Reasoning about location of robot-operated object based on probabilistic ontologies
Authors: Ge Yueguang , Zhang Shaolin , Cai Yinghao , Lu Tao , Wen Dayong , Wang Haitao , Zheng Zekai , Wang Shuo
Published: February 2022

Background: A robot needs to acquire the location of objects when performing daily tasks. Compared to industrial robots, a service robot faces a more complex and unstructured working environment where the location of the target object is usually uncertain. For example, due to diversity in personal habits and seasons, apples may be located in refrigerators, tables, or other places in the living environment.

Methods: We propose a novel method for semantic localization of the robot-operated object based on probabilistic ontologies (PR-OWL) and multi-entity Bayesian networks (MEBN). The probabilistic web ontology language is used to describe and model the highly uncertain knowledge about the storage location of objects in the human household environment. Furthermore, the target location is inferred based on the multi-entity Bayesian network.

Results: The proposed method is capable to adapting to environmental changes and achieves reliable probability estimation of object location. Experiments on simulated robotic tasks verify the effectiveness of the method.

Conclusions: We show that applying PR-OWL combined with MEBN to locate the target object for the robot is feasible， which can improve the cognitive and self-adaptive ability of the robot.
Cost of Goods Analysis Facilitates an Integrated Approach to Identifying Alternative Synthesis Methodologies for Lower Cost Manufacturing of the COVID-19 Antiviral Molnupiravir
Authors: Peterson Christopher , Paria Sayan , Deshpande Anita , Ahmad Saeed , Harmon Andrew , Dillon John , Laird Trevor
Published: February 2022

Orally delivered drugs offer significant benefits in the fight against viral infections, and cost-effective production is critical to their impact on pandemic response in low- and middle-income countries. One example, molnupiravir, a COVID-19 therapy developed by Emory, Ridgeback, and Merck & Co., had potential to benefit from significant cost of goods (COGs) reductions for its active pharmaceutical ingredient (API), including starting materials. A holistic approach to identifying, developing, and evaluating optimized synthetic routes, which includes detailed COGs modeling, provides a rapid means to increase the availability, uptake and application of molnupiravir and other antivirals in global markets.

Identification and development of alternate processes for the synthesis of molnupiravir has been conducted by the Medicines for All Institute at Virginia Commonwealth University (M4ALL) and the Green and Turner Labs at the University of Manchester. Both groups developed innovative processes based on synthetic route design and biocatalysis aimed at lowering costs and improving global access. The authors then performed COGs modeling to assess cost saving opportunities. This included a focus on manufacturing environments and facilities amenable to global public health and the identification of key parameters using sensitivity analyses.

While all of the evaluated routes provide efficiency benefits, the best options yielded 3-6 fold API COGs reductions leading to treatment COGs as low as <$3/regimen. Additionally, key starting materials and cost drivers were quantified to evaluate the robustness of the savings. Finally, COGs models can continue to inform the focus of future development efforts on the most promising routes for additional cost savings.

While the full price of a treatment course includes other factors, these alternative API synthetic approaches have significant potential to help facilitate broader access in low- and middle-income countries. As other promising therapeutics are developed, a similar process could enable rapid cost reductions while enhancing global access.
Co-constructing conversations about suicide: the Meeting Space Framework
Authors: Rebair Annessa
Published: February 2022

This article draws on research conducted for the author's doctoral thesis. It presents the development of the Meeting Space Framework to address what is needed to engage in meaningful conversations about suicide, from the perspective of student nurses. An interpretive methodology of constructivist grounded theory was used, underpinned by the theoretical perspective of symbolic interactionism. The core category of Meeting Spaces resulted; engaging in meaningful conversations about suicide is co-created in illuminating space within the context of a human pivotal encounter (positive) as opposed to an unceremonious pivotal encounter (negative). A certain kind of space is required to support engagement in meaningful conversations about suicide. It requires humanness and an intention and ability to see the whole person beyond the limiting word of ‘suicide’.
Decision-making in the management of complicated crown fractures in children
Authors: Politi Ioanna , Leith Rona
Published: February 2022

Complicated crown fractures of permanent teeth following dental trauma in children are a common presentation in the dental practice. The prognosis of these teeth largely depends on the emergency management provided by the dentist. Treatment options include direct pulp capping and partial pulpotomy. While both have been suggested as possible vital pulp therapies for the management of complicated crown fractures, there are no clear recommendations as to when each procedure is indicated to aid the clinician in decision making. This narrative review aims to provide evidence-based recommendations for the optimal management of complicated crown fractures in children. The factors affecting success rates of both direct pulp capping and partial pulpotomy are discussed and a step-by-step guide to carrying out a partial pulpotomy is presented.

CPD/Clinical Relevance: This article will assist clinicians in making an evidence-based decision for the optimal management of complicated crown fractures of permanent teeth in children.
Resource use within a multidisciplinary foot team clinic
Authors: Liew Huiling , Bates Maureen , Vas Prashanth , Rashid Hisham , Kavarthapu Venu , Edmonds Michael , Manu Chris
Published: February 2022

Objective:

The establishment of multidisciplinary foot team clinics reduces the risk of amputation, but little is known about its resource requirement. This study evaluates the service's resource use for first visit attendees to an established multidisciplinary foot team clinic.

Method:

A retrospective evaluation was performed for new referrals to the clinic over six months, including demographics, resource use and clinical outcome. Data were extracted electronically with retrospective review of electronic clinical notes.

Results:

A total of 240 first visit attendees were analysed. Mean age was 64±15years, 63% were male, 72% had type 2 diabetes, 16% had type 1 diabetes, 15% had a previous amputation, and 40% had a previous ulceration. Common presentations were ulcers (62%), osteomyelitis (11%), Charcot foot (19%), foot ischaemia (17%), post-surgical wounds (13%), and osteomyelitis (11%). At first attendance, 79% of patients required specialist services including diabetologist (45%), joint vascular review (23%), joint orthopaedics services (8%), dermatologist (2%), and orthotics services (1%). A total of 4% of patients had complex debridement, 0.4% total nail excision, 0.8% pus drainage, 3% cast-related procedures, and 1% vacuum-assisted dressing. Of the patients, 4% were admitted to hospital, 38% had vascular duplex investigations, 7% had a deep vein thrombosis scan, 16% had magnetic resonance imagine (MRI), and 5% had a bone scan.

Conclusion:

A functional multidisciplinary foot team clinic requires significant resources—both clinical and administrative—for prompt investigations and revascularisation to sustain low amputation rates. Regular appraisal of resource use helps with clinic and pathway planning.
The efficacy of sodium hypochlorite antiseptic: a double-blind, randomised controlled pilot study
Authors: Serena Thomas E , Serena Laura , Al-Jalodi Omar , Patel Keyur , Breisinger Kristy
Published: February 2022

Objective:

According to a recent clinical trial, 82% of hard-to-heal wounds harbour levels of bacteria that impede healing. A follow-up analysis of trial data revealed that the use of antiseptic cleansers did not correlate with bacterial burden. At a minimum, these findings suggest the need for clinical research into the efficacy of antiseptics in reducing bacterial burden. Evidence supporting the bacterial killing ability of antiseptics is largely derived from preclinical and laboratory studies. Few clinical trials have examined bacterial levels and healing rates in hard-to-heal wounds. Fortunately, the advent of fluorescence imaging to detect bacterial burden has simplified the conduct of clinical research examining the effectiveness of antiseptics in the clinic setting. The aim of this study was to evaluate the efficacy of a modified sodium hypochlorite (NaOCl) solution in reducing wound size and bacterial load in hard-to-heal wounds.

Method:

In this randomised, double-blind pilot study, patients were randomised to one of two groups: daily wound cleansing with either normal saline solution (NSS) or NaOCl. Patients and investigators were blinded to the allocation. All wound types were included.

Results:

A total of 16 patients consented to participate. At the initial visit, the target ulcer was measured and a fluorescence image to evaluate bacterial load obtained. The wound was then cleansed with either NSS or NaOCl and fluorescence imaging repeated. Patients cleansed the wound daily in accordance with the randomisation schedule. They returned to the clinic weekly for four weeks, and on each visit the wound was measured and a fluorescence image captured. Patients receiving NaOCl had a greater percent reduction in wound area versus NSS; although the first phase of the study was not powered for statistical significance, there was a strong trend favouring NaOCl. In addition, there was greater bacterial reduction in the NaOCl group.

Conclusion:

Based on the results of this pilot study, enrolment has continued in order to increase the study's power. This pilot study suggests that sodium hypochlorite is efficacious in reducing bacterial burden and promoting healing.
ALLOPURINOL
Authors: Rees Sharon
Published: February 2022

In this column, Sharon Rees aims to refresh knowledge and interest in some of the commonly used drugs in a series of tweets. This month she is talking about #allopurinol
Prescribing errors in general practice
Authors: McCutcheon Jennifer
Published: February 2022

Nurses, pharmacists and allied health professionals are increasingly becoming prescribers and many of them work autonomously in general practice. Prescribing professionals have a duty to understand what a prescribing error is, common examples of errors in practice, how they are prevented and how they can be investigated and reported should they occur.
Electrically pumped laser transmitter integrated on thin-film lithium niobate
Authors: Shams-Ansari Amirhassan , Renaud Dylan , Cheng Rebecca , Shao Linbo , He Lingyan , Zhu Di , Yu Mengjie , Grant Hannah R. , Johansson Leif , Zhang Mian , Lončar Marko
Published: February 2022

Integrated thin-film lithium niobate (TFLN) photonics has emerged as a promising platform for the realization of high-performance chip-scale optical systems. Of particular importance are TFLN electro-optic modulators featuring high-linearity, low driving voltage and low propagation loss. However, a fully integrated system requires integration of high power, low noise, and narrow linewidth lasers on TFLN chips. Here we achieve this goal, and demonstrate integrated high-power lasers on TFLN platform with up to 60 mW of optical power in the waveguides. We use this platform to realize a high-power transmitter consisting of an electrically pumped laser integrated with a 50 GHz modulator.
Bifidobacterium lactis BL-99 modulates intestinal inflammation and functions in zebrafish models
Authors: Chen Meng , Liu Chinfeng , Dai Mingzhu , Wang Qinwen , Li Chunqi , Hung Weilian
Published: February 2022

This study was designed to explore the therapeutics and the mechanisms of a patented and marked gastric acid and intestine juice-resistant probiotics Bifidobacterium lactis BL-99 (B. lactis BL-99) on the intestinal inflammation and functions in the zebrafish models. After feeding for 6 hours, B. lactis BL-99 was fully retained in the larval zebrafish intestinal tract and stayed for over 24 hours. B. lactis BL-99 promoted the intestinal motility and effectively alleviated aluminum sulfate-induced larval zebrafish constipation (p < 0.01). Irregular high glucose diet induced adult zebrafish intestinal functional and metabolic disorders. After fed with B. lactis BL-99, IL-1β gene expression was significantly down-regulated, and IL-10 and IL-12 gene levels were markedly up-regulated in this model (p < 0.05). The intestinal lipase activity was elevated in the adult zebrafish intestinal functional disorder model after B. lactis BL-99 treatment (p < 0.05), but tryptase content had no statistical changes (p > 0.05). B. lactis BL-99 improved the histopathology of the adult zebrafish intestinal inflammation, increased the goblet cell numbers, and up-and-down metabolites were markedly recovered after treatment of B. lactis BL-99 (p < 0.05). These results suggest that B. lactis BL-99 could relieve intestinal inflammation and promote intestinal functions, at least in part, through modulating intestinal and microbial metabolism to maintain intestinal health.
The clean energy claims of BP, Chevron, ExxonMobil and Shell: A mismatch between discourse, actions and investments
Authors: Li Mei , Trencher Gregory , Asuka Jusen
Published: February 2022

The energy products of oil and gas majors have contributed significantly to global greenhouse gas emissions (GHG) and planetary warming over the past century. Decarbonizing the global economy by mid-century to avoid dangerous climate change thus cannot occur without a profound transformation of their fossil fuel-based business models. Recently, several majors are increasingly discussing clean energy and climate change, pledging decarbonization strategies, and investing in alternative energies. Some even claim to be transforming into clean energy companies. Given a history of obstructive climate actions and “greenwashing”, there is a need to objectively evaluate current and historical decarbonization efforts and investment behavior. This study focuses on two American (Chevron, ExxonMobil) and two European majors (BP, Shell). Using data collected over 2009–2020, we comparatively examine the extent of decarbonization and clean energy transition activity from three perspectives: (1) keyword use in annual reports (discourse); (2) business strategies (pledges and actions); and (3) production, expenditures and earnings for fossil fuels along with investments in clean energy (investments). We found a strong increase in discourse related to “climate”, “low-carbon” and “transition”, especially by BP and Shell. Similarly, we observed increasing tendencies toward strategies related to decarbonization and clean energy. But these are dominated by pledges rather than concrete actions. Moreover, the financial analysis reveals a continuing business model dependence on fossil fuels along with insignificant and opaque spending on clean energy. We thus conclude that the transition to clean energy business models is not occurring, since the magnitude of investments and actions does not match discourse. Until actions and investment behavior are brought into alignment with discourse, accusations of greenwashing appear well-founded.
Implementation fidelity of tuberculosis preventive therapy for under five children exposed to sputum smear positive pulmonary tuberculosis in Kaski district, Nepal: An implementation research
Authors: Ghimire Ashmita , Mahendradhata Yodi , Paudel Sagun , Lama Yonzon Chhoden , K. C. Bhuvan , Sharma Sushmita , Utarini Adi
Published: February 2022

Introduction

In line with the WHO recommendation, Nepal has started implementing Tuberculosis prevention therapy (TBPT) for under five children exposed to Sputum Smear Positive Pulmonary Tuberculosis, as one of the strategies for prevention, care and control of TB. Implementation fidelity study is important to assess on what extent preventive program is being implemented. The objective of the study measured the implementation fidelity of TBPT program Kaski district, Nepal.

Methods

We used a mixed-method explanatory sequential design study. Quantitative data were collected through retrospective review of records from April 2018 to May 2019 and level of adherence was established. Moderating factors influencing the implementation of TBPT were TBPT were assessed qualitatively. Sixteen in-depth interviews and a focus group discussion was conducted purposively with responsible stakeholders. The study was guided by the Conceptual Framework for Implementation Fidelity (CFIR) developed by Carroll.

Results

The majority of the components of the TBPT program were found to be implemented with a moderate level of fidelity. The proportion of under five years children initiate and complete the full course of TBPT was 72.5% and 75.86% respectively. The proportion of index cases traced for household contact, contact tracing within two months and timely initiation of therapy within two months were 54.19%, 82.73% and 86.20%. Moderating factors identified in the implementation of the program were contact tracing and enrollment, partnership and ownership, training resources, medication, awareness and information dissemination.

Conclusion

The TBPT program is being moderately implemented in Kaski districts. Addressing the key challenges identified in contact tracing, partnership/ownership, incentives, training and knowledge of health workers results in more identification of children eligible for TBPT.
Identification of a novel stripe rust resistance gene from the European winter wheat cultivar ‘Acienda’: A step towards rust proofing wheat cultivation
Authors: Grover Gomti , Sharma Achla , Mackay Ian , Srivastava Puja , Kaur Satinder , Kaur Jaspal , Burridge Amanda , Allen Sacha Przewieslik , Bentley Alison R. , Chhuneja Parveen , Bains N. S.
Published: February 2022

All stage resistance to stripe rust races prevalent in India was investigated in the European winter wheat cultivar ‘Acienda’. In order to dissect the genetic basis of the resistance, a backcross population was developed between ‘Acienda’ and the stripe rust susceptible Indian spring wheat cultivar ‘HD 2967’. Inheritance studies revealed segregation for a dominant resistant gene. High density SNP genotyping was used to map stripe rust resistance and marker regression analysis located stripe rust resistance to the distal end of wheat chromosome 1A. Interval mapping located this region between the SNP markers AX-95162217 and AX-94540853, at a LOD score of 15.83 with a phenotypic contribution of 60%. This major stripe rust resistance locus from ‘Acienda’ has been temporarily designated as Yraci. A candidate gene search in the 2.76 Mb region carrying Yraci on chromosome 1A identified 18 NBS-LRR genes based on wheat RefSeqv1.0 annotations. Our results indicate that as there is no major gene reported in the Yraci chromosome region, it is likely to be a novel stripe rust resistance locus and offers potential for deployment, using the identified markers, to confer all stage stripe rust resistance.
Risk of Metachronous Colorectal Advanced Neoplasia and Cancer in Patients With 3–4 Nonadvanced Adenomas at Index Colonoscopy: A Systematic Review and Meta-Analysis
Authors: Park Suyeon , Jeon Seong Ran , Kim Hyun Gun , Jung Yunho , Kwak Min-Seob , Kim Su Young , Kim Jong Wook , Nam Seung-Joo , Oh Eun Hye , Park Seon-Young , Park Soo-Kyung , Byeon Jeong-Sik , Boo Sun-Jin , Baek Dong Hoon , Yoon Soon Man , Chun Jaeyoung , Lee Jooyoung , Choi Miyoung
Published: February 2022

INTRODUCTION:

This systematic review and meta-analysis evaluated the available evidence on the risk of metachronous advanced neoplasia (AN) and colorectal cancer (CRC) in patients with 3–4 nonadvanced adenomas (NAAs).

METHODS:

We searched MEDLINE, EMBASE, and Cochrane Library databases up to January 2021 for studies evaluating metachronous AN and CRC risk by comparing 3 groups (1–2 vs 3–4 vs ≥5 NAAs) at index colonoscopy. The estimates for risk of metachronous AN and CRC were evaluated using random-effects models.

RESULTS:

Fifteen studies (n = 36,375) were included. The risk of metachronous AN was significantly higher in the 3–4 NAAs group than in the 1–2 NAAs group (relative risk [RR] 1.264, 95% confidence interval [CI] 1.053–1.518, P = 0.012; I2 = 0%); there was no difference between the ≥ 5 NAAs and 3–4 NAAs groups (RR 1.962, 95% CI 0.972–3.958, P = 0.060; I2 = 68%). The risks of metachronous CRC between the 1–2 NAAs and 3–4 NAAs groups (RR 2.663, 95% CI 0.391–18.128, P = 0.317; I2 = 0%) or the 3–4 NAAs and ≥ 5 NAAs groups (RR 1.148, 95% CI 0.142–9.290, P = 0.897; I2 = 0%) were not significantly different.

DISCUSSION:

Although the risk of metachronous AN was greater in the 3–4 NAAs group than in the 1–2 NAAs group, the risk of metachronous AN and CRC between the 3–4 NAAs and ≥ 5 NAAs groups was not different. This suggests that further studies on metachronous AN and CRC risk in the 3–4 NAAs group are warranted to confirm a firm ≥5-year interval surveillance colonoscopy.
Material Culture and (Forced) Migration: Materialising the transient
Authors: Lauser Andrea , Fuhse Antonie , Bräunlein Peter J.
Published: February 2022

Material Culture and (Forced) Migration argues that materiality is a fundamental dimension of migration. During journeys of migration, people take things with them, or they lose, find and engage things along the way. Movements themselves are framed by objects such as borders, passports, tents, camp infrastructures, boats and mobile phones. This volume brings together chapters that are based on research into a broad range of movements – from the study of forced migration and displacement to the analysis of retirement migration. What ties the chapters together is the perspective of material culture and an understanding of materiality that does not reduce objects to mere symbols. Centring on four interconnected themes – temporality and materiality, methods of object-based migration research, the affective capacities of objects, and the engagement of things in place-making practices – the volume provides a material culture perspective for migration scholars around the globe, representing disciplines such as anthropology, sociology, contemporary archaeology, curatorial studies, history and human geography. The ethnographic nature of the chapters and the focus on everyday objects and practices will appeal to all those interested in the broader conditions and tangible experiences of migration.
Effect of Types and Dosages of Foliar Fertilizers on Morphology and Production of Clitoria ternatea
Authors: Sariffudin Apriyani Nur , Umami Nafiatul , Suhartanto Bambang , Suwignyo Bambang , Kustantinah Kustantinah
Published: February 2022

The aim of this study was to determine effect of types and dose levels of foliar fertilizers on  morphology and production of Clitoria ternatea. This study was conducted from September to November 2020 at Forage Research Garden for Animal Feed and Pasture, Faculty of Animal Science, Gadjah Mada University, Yogyakarta. Materials used were Clitoria ternatea, liquid organic fertilizer of rabbit and gandasil D fertilizer. This study was designed in a Completely Randomized Design (CRD) with factorial pattern of 2x4. The fertilizer dosages were: 0,1.5,3.0 and 4.5 g/l/plot. The parameters measured were plant height, stem diameter, leaf area, number of branches, fresh and dry matter productions. Data were analyzed by the analysis of variance at 5%, with Duncan's Multiple Range Test (DMRT). Results showed that types of foliar fertilizers did not affect morphological characteristics and production of Clitoria ternatea (P>0.05), but the fertilizer dosages had significant effect (P<0.05) on morphological characteristics except for leaf area and production of Clitoria ternatea. The higher the dose level of foliar fertilizer the greater the plant height, stem diameter and number of branches. Dosage of 4.5 g/l/plot resulted in the highest plant height, stem diameter and number of branches each 160.02, 1.14 cm and 18.96 branches, respectively. Dosage of4.5 g/l/plot gave the highest fresh and dry matter production of 19.22 and 16.75 tons/ha. It is concluded that increasing the dosage level of foliar fertilizer up to 4.5 g/l/plot resulted in an increased quantity measures of several morphological characteristics and production.
Bone metabolism in diabetes mellitus: focus on vitamin K2
Authors: Radugin F. M. , Karonova T. L.
Published: February 2022

Diabetes mellitus (DM) type 2 is reported to be among the most common diseases both worldwide and in Russian Federation, whereby chronic implications that develop under hyperglycemia pose a serious socioeconomic problem. Besides of classic microvascular complications like diabetic retinopathy, nephropathy and polyneuropathy it’s recently worthy of note the presence of high fracture risk in DM type 2 even in normal bone mass density, known as “diaporosis” or “diabetoporosis” considered as another DM complication. It is well known that osteoporosis is reported to be widespread disease as same as DM type 2 and likewise is a widely abundant in older age that makes their combination is really possible in a single patient. Taking into account high social value and disability due to osteoporotic fractures and chronic DM type 2 complications it becomes necessary to continue physiologic and biochemical basis investigations of bone formation and remodeling and pathogenesis of osteoporosis development in the context of chronic hyperglycemia. One of the fairly new factors which the experts believe it is link between impaired glucose metabolism and bone remodeling is osteocalcin which concentration is dependent on vitamin K2 maintenance considered as a potential agent in osteoporotic fractures prevention. In this review current information on vitamin K2 influence on bone status and possibility of using this nutrient in clinical practice in the focus on patients with DM will be covered.
Empatía y componentes de la empatía en estudiantes mexicanos de enfermería: estudio transversal
Authors: Andrade Valle Irma , Facio Arciniega Susana , Alemán de la Torre Laura , Quiroz Guerra Alma Rosa , Calzadilla Núñez Aracelis , Díaz-Narváez Víctor
Published: February 2022

Introducción: La empatía es importante para el profesional de enfermería y debe ser incorporada a la formación de los estudiantes de pregrado a partir de evidencias empíricas sólidas. El objetivo de este trabajo fue caracterizar la situación empática de los estudiantes examinados. Materiales y métodos: Es un trabajo exploratorio, transversal, con 331 estudiantes de la Escuela de Enfermería de la Universidad Autónoma de Coahuila, México. Se aplicó la Escala de Empatía Médica de Jefferson (versión S), adaptada y validada para estudiantes de enfermería. Se estimó el alpha de Cronbach y correlación intraclase para estudiar la fiabilidad de los datos. Se aplicó un análisis de varianza bifactorial para determinar diferencias entre cursos, géneros e interacción entre factores, modelos de regresión de las medias de la empatía a través de los cursos. Resultados: Existe confiabilidad adecuada de los datos. Hay diferencias entre los cursos para la empatía y el componente cuidado con compasión, entre géneros en los componentes “cuidado con compasión y habilidad para entender al otro”. Bajo crecimiento empático que no se ajusta al modelo de declinación. Conclusión: El comportamiento empático de los estudiantes obedece a modelos no lineales; no se manifiesta el fenómeno de declinación empática: el crecimiento de la empatía y de sus componentes es bajo; el crecimiento de la empatía en el componente “cuidado con compasión” es mayor en hombres; en el componente “toma de perspectiva del paciente” es ma-yor en mujeres y la habilidad para entender a los demás es baja y semejante entre géneros.
Efectos del consumo de alimentos en la concentración de hemoglobina y el riesgo de anemia infantil en el Perú – 2018
Authors: Calatayud Mendoza Alfredo Pelayo , Inquilla Mamani Juan , Paredes Mamani René Paz
Published: February 2022

Objetivo: Caracterizar y medir el efecto del consumo de alimentos sobre la concentración de hemoglobina y el riesgo de armenia en niños menores de tres años en el Perú. Materiales y Métodos: Se empleó datos de corte transversal de la Encuesta Nacional de Hogares y la Encuesta Demográfica y de Salud Familiar ENDES del año 2018. En la estimación del efecto del consumo de alimentos sobre la concentración de hemoglobina se empleó el modelo de regresión lineal múltiple; mientras que para medir el efecto de consumo de alimentos sobre el riego de anemia se empleó el modelo de regresión probit. Resultados. Se encontró que el consumo de lechuga, apio y beterrega (verduras), hígado (carne roja), papaya (fruta) contribuyen positivamente sobre la concentración de hemoglobina y la reducción del riesgo de anemia. La papa (tubérculo) contribuye positivamente en el incremento de la hemoglobina y la reducción del riesgo de anemia para niveles de consumo por debajo de 50 kilogramos por año. Entre las variables de control resultaron altanamente significativos las características biológicas de la madre y el niño, las características socioeconómicas del hogar, y las características de la región y comunidad. Conclusión. El mayor consumo de hígado de res, lechuga y beterraga produce mayores niveles de hemoglobina, mientras el consumo de papa por debajo de 50 kg en promedio anual contribuye a la reducción del riesgo de anemia, y mayor consumo de apio y papaya genera una menor probabilidad de riesgo de contraer anemia.
Hayama Yoshiki’s “The Prostitute” in Taiwanese and Manchukuo Proletarian Literature
Authors: Blahota Martin
Published: February 2022

In the 1920s and 1930s, the Japanese proletarian literary movement had an enormous impact on East Asian writers, who often translated and adapted Japanese tales. Amongst them, Hayama Yoshiki’s 1925 short story “Inbaifu” (The Prostitute) enjoyed great popularity. This paper focuses on the Taiwanese writer Lang-shi-sheng’s adaptation of “Inbaifu”, the 1935 “Yami” (Darkness), and Manchukuo writer Yuan Xi’s adaptation of the same Japanese source text, the 1938 short story “Shi tian” (Ten Days). By comparing the Taiwanese and Manchukuo stories, this paper suggests that both versions of “Inbaifu” reflect the Japanese debate on proletarian literature that was fashionable in East Asia in the 1930s. However, by resetting the stories in Taiwan and Manchukuo, respectively, the authors created cultural products that defy borders and simple nationalist interpretations.
European Higher Education Area, internationalization and students’ mobility in 21st century
Authors: Kavasakalis Aggelos , Gkiza Theodora
Published: February 2022

Higher Education Institutions (HEIs) seem to be influenced by the evolutions of globalization, to modernize and operate according to the knowledge society and therefore preparing and equipping students with the appropriate knowledge and skills required in order to respond to new situations imposed by the modern globalized environment. A principal axis is the internationalization of the teaching and learning provided in order to increase the competitiveness among institutions, improve the quality of the provided services and lastly integrate an international as well as intercultural dimension in the purpose, the functions and the mission of an institution (De Wit, 2015; Knight, 2004). The aim of the present article is to provide a theoretical reflection on internationalization and student mobility (which is an internationalization policy) in European Higher Education Area in the 21st century. The first section will attempt to delineate the concept of internationalization and its modern dimensions in the HE, while referring to the ways that is promoted within the European Area. The second section focuses on student mobility in the 21st century. First, there is a brief description of the history of mobility and then the relationship between mobility and the Bologna Process is outlined. In addition, student mobility programs are described as well as the evaluation of students' experiences who participated in those programs, as shown in relevant research. Reference is also made to student mobility at the time of Covid-19 spread. Lastly, in the third section an attempt is made to link the processes of internationalization and mobility in Higher Education in Europe.
Making Sense of Chondrite Meteorites
Authors: Herndon J. Marvin
Published: February 2022

I describe the simplification of multitudes of complex data on hundreds of chondrite meteorites to obtain a fundamental relationship that underlies processes during solar system formation. From the relationship derived, generally, it can be concluded that only three processes, operant during solar system formation, are responsible for the diversity of matter in the solar system, as well as for planetary compositions , internal-structures, dynamics and magnetics: (1) Condensation at very high-pressures; (2) Condensation at very low-pressures; and (3) Scouring of the inner solar system by the T-Tauri eruptions during thermonuclear ignition of the sun.