bluuebunny/crossref_metadata_2025 huggingface dataset:
Specialist Palliative Care and Dementia: Staff Challenges and Learning Needs
Authors: Currie S.J. , Curtin C. , Timmons S.
Published: June 2023

Objective: This study explored the perspectives of specialist palliative care (SPC) teams in Ireland, in relation to personal learning needs and education regarding dementia care. Methods: This mixed-methods study involved a survey and focus group. SPC staff were recruited through a professional palliative care society and via hospices in 4 regions. Survey items included challenges in clinical care, personal learning needs, and preferred modes of educational delivery. Quantitative data analysis was descriptive; open-answer survey questions and the focus group transcript underwent thematic analysis. Results: In total, 76 staff completed surveys and rated the following as most challenging: timely access to community agency and specialist support; and managing the needs of people with dementia (PwD). Respondents volunteered additional challenges around the timing/duration of SPC involvement, prognostication, and inadequate knowledge of local services. Staff ranked learning needs as highest in: nonpharmacological management of noncognitive and cognitive symptoms; differentiation of dementia subtypes; and pharmacological management of cognitive symptoms. The focus group (n = 4) gave deeper perspectives on these topics. Overall, 79.2% of staff preferred formal presentations by dementia-care specialists and 76.6% preferred e-learning. Conclusion: Several dementia-care challenges and learning needs are identified by SPC staff, as above. These can inform the design and delivery of tailored education programs for SPC staff. There is also a need for closer working between dementia services and SPC services to provide integrated, holistic care for PwD. One aspect of achieving this is greater awareness of local dementia-care services among SPC staff, and vice versa.
Research and therapeutic applications of silk proteins in cancer
Authors: Kumari Neema , Pullaguri Narasimha , Sahu Vikas , Ealla Kranti Kiran Reddy
Published: June 2023

Despite the availability of advanced treatments, cancer remains the second leading cause of death worldwide. This is due to the many challenges prevailing in the research field and cancer therapy. Resistance to therapy and side effects provide major hindrances to recovery from cancer. As a result, in addition to the aim of killing cancer cells, the focus should also be on reducing or preventing side effects of the treatment. To enhance the effectiveness of cancer treatment, many researchers are studying drug delivery systems based on silk proteins: fibroin and sericin. These proteins have high biocompatibility, biodegradability, and ease of modification. Consequently, many researchers have developed several formulations of silk proteins such as scaffolds, nanoparticles, and hydrogels by combining them with other materials or drugs. This review summarizes the use of silk proteins in various forms in cancer research and therapy. The use of silk proteins to study cancer cells, to deliver cancer drugs to a target site, in cancer thermal therapy, and as an anti-cancer agent is described here.
Pay Transparency: Why it is Important to be Thoughtful and Strategic
Authors: Avdul David N. , Martin William Marty , Lopez Yvette P.
Published: June 2023

Pay transparency is quickly ascending to the forefront of human resources compensation issues. Employees—especially younger employees—at organizations and society in general are seeking fairer outcomes and more transparency with compensation falls in line with those expectations. Governments are responding by drafting and passing new pay transparency legislation. Based on the research conducted, pay transparency can yield benefits such as helping to close pay gaps, reducing employee turnover, and elevating trust with management and others, but can also create confusion and negative outcomes. This article provides a summary of what pay transparency is, why it is gaining in importance, how it impacts organizations and where the trend may be heading. A list of strategic recommendations is offered for organizational leaders to consider when navigating through an environment with greater pay transparency.
Gender and Ethnic Intersectionality in Solicitors’ Careers, 1970 to 2016
Authors: Valizade Danat , Tomlinson Jennifer , Muzio Daniel , Charlwood Andy , Aulakh Sundeep
Published: June 2023

This article provides new insights into the intersection of gender and ethnic inequalities in the solicitors’ profession. Using administrative records spanning the entire population of practising solicitors in England and Wales, we analyse structural changes over successive cohorts of solicitors and identify four distinctive employment profiles: high-street solicitors, city solicitors, corporate fast-track and in-house. We show how solicitors with single or multiple characteristics associated with disadvantage are located in different employment profiles and how this changes over time. Demonstrating originality and the value of an intersectional analysis, we find that while ethnic stratification within solicitor careers decreases, stratification by gender remains constant. We find that in a period of rapid expansion, minority ethnic men become much better integrated into the most prestigious career profile in the profession – the corporate fast-track – compared with white women who are both earlier entrants to and numerically dominant in the profession.
‘Getting Rich is Glorious’: Environmental Values in the People's Republic of China
Authors: Harris Paul G.
Published: June 2023

Pollution and overuse of resources in China have profound implications for the Chinese people and the world. Globalisation may be partly to blame for this situation, but it is hardly the only explanation. China has been overusing its resources for centuries. Traditional values appear to offer environmentally benign guidance for China's economic development, but they are largely impotent in the face of now-pervasive values manifested in Western-style consumption. Government policies go some way toward addressing this problem, but what may be required is a new set of values that brings self-interest and environmental protection into common cause.
When ‘The Environment’ Comes to Visit: Local Environmental Knowledge in the Far North of Russia
Authors: Karjalainen Timo Pauli , Habeck Joachim Otto
Published: June 2023

Based on field research in villages and towns in the Komi Republic (northeastern European Russia), this article compares the perception of the environment with environmental knowledge, and examines their interrelations in local contexts. An individual's perception of the environment is embedded in his/her everyday engagement with the surroundings (‘the environment’ as seen from within). Environmental knowledge is of more cognitive character: it originates mainly from outside the context of everyday life and is imparted via various forms of communication (‘The Environment’ as seen from the outside). From the interplay of these two levels arises what we call local environmental knowledge, a kind of knowledge which has its own moral and symbolic dimension within the social, cultural and political setting. Similarly, the concept of environmentalism is increasingly recognised as a wide diversity of ‘green’ views and actions rather than as a single project of a globally consistent normative character; thus there is a need to examine the contextuality of environmental concern. Our findings explain the failure of the ‘information deficit’ model, according to which the dissemination of scientific knowledge about environmental problems should result in local inhabitants changing their attitudes towards ‘The Environment’. Instead, our findings support the insight that, rather than accepting environmental knowledge from external sources as a factual given, individuals restate it in terms of their everyday life contexts and local discourses about socio-political issues.
Some Theoretical Foundations for Radical Green Politics
Authors: Carter Alan
Published: June 2023

On the basis of our apparent obligations to future generations, it would seem that we are morally obliged to reduce the risk our environmentally destructive behaviour poses for their well-being. But if, rather than choosing to destroy the environment, we are in fact driven to do so, then any obligation to reduce our environmental impact requires an understanding of the mechanism driving our behaviour. This article argues that the State-Primacy Theory provides a plausible explanation for the nature of that mechanism, and concludes that the most common strategies offered as a response to our environmental impact are most likely to be insufficiently radical to meet our seeming obligations effectively.
Environmental Pollution and Professional Responsibility: Ibsen's A Public Enemy as a Seminar on Science Communication and Ethics
Authors: Zwart Hub
Published: June 2023

Dr Stockmann, the principal character in Henrik Ibsen's A Public Enemy, is a classic example of a whistle-blower who, upon detecting and disclosing a serious case of environmental pollution, quickly finds himself transformed from a public benefactor into a political outcast by those in power. If we submit the play to a ‘second reading’, however, it becomes clear that the ethical intricacies of whistle-blowing are interwoven with epistemological issues. Basically, the play is about the complex task of communicating scientific (notably microbiological) data to lay audiences. This becomes even more apparent when we realise that Stockmann was a contemporary of real ‘microbe hunters’ such as Pasteur and Koch. The play's basic message is that epoch-making scientists (such as Pasteur and Koch) not only produced convincing and reliable data from a scientific point of view, but also acquired the skills and insights needed to enter into a dialogue with their cultural and societal environment.
Reproductive Liberty and Overpopulation: A Response
Authors: Warner Stanley
Published: June 2023

This appraisal of Carol A. Kates’ ‘Reproductive Liberty and Overpopulation’ challenges her call for world-wide population control measures – using compulsory methods if necessary – to save the world's environment. The most successful part of Kates’ paper is her argument that reproductive rights are not indefeasible and nonnegotiable, but that like many rights, they are conditional and open to a balancing of individual freedom against collective community interests. But her advocacy of mandatory state population controls is flawed in several respects. First, she underestimates the force of the emerging consensus for voluntary population reductions through policies that empower women. Second, she walks on difficult ethical grounds. Are compulsory controls on reproduction ethically justified simply because humans are loathe to take the alternative route of curtailing their ‘individualistic’ ‘materialistic’ appetites for more economic growth and consumption? Third, Kates fails to recognise that her search for measures that immediately and directly reverse population growth would necessitate coercing an entire generation of women toward zero reproduction in order for death rates to have their effect. Lastly, problems with the feasibility of her plan and the absence of international support make it unlikely it will ever come to pass. Alternatives to Kates’ policies are discussed at the close.
Experimental study on acoustic emission stress memory function of rock-like specimens under uniaxial compression
Authors: Tian Yong , Yu Rangang , Chen Fanxiu , Meng Fanzhen , Zhang Zhaojun
Published: June 2023

The Kaiser effect in rock acoustic emission (AE) test is the most direct manifestation of rock memory function. This article focuses on the influence of different deformation stages and different historical stress conditions on stress memory function, and conducts AE testing of rock-like specimens. It explained the stress memory function in AE testing from the perspectives of crack propagation and damage accumulation. The crack initiation stress σci and crack damage stress σcd of specimens were obtained based on the stress-strain curve method, and the different deformation stages were divided. The damage evolution coefficient [Formula: see text] was proposed to measure the size of the stable development range of damage based on the normalized crack initiation and crack damage stress. The historical stress in the elastic stage could be easily identified from the Kaiser effect during the reloading process, even if the time interval reached 120 hours. The Felicity effect appeared during the reloading process when the historical stress was in the stage of stable crack propagation, and the FR value showed a decreasing trend with the extension of the time interval between loading tests. The loading history in the elastic stage was a training for the AE stress memory function under complex historical stress conditions, which restored the Kaiser effect in the stage of stable crack propagation. The distribution of AE events and CT scanning results were also analyzed in the article, and the damage accumulation information characterized by both are basically consistent. The double Kaiser effect phenomenon appeared in the AE test under complex historical stress conditions, although the criterion for discriminating the AE signal at the Kaiser effect point corresponding to the lower stress remained to be further studied and verified.
The Impact of Bacteriospermia on Semen Parameters Among Infertile Egyptian Men: A Case–Control Study
Authors: Shash Rania Yahia Mohammad , Mohamed Gehad Attia Abdallah , Shebl Salah E. , Shokr Mohamed , Soliman Soliman Aref
Published: June 2023

This study aimed to detect the impact of bacteriospermia on semen parameters and sperm DNA fragmentation. This prospective case–control study was conducted over a period of 9 months. Samples were collected from andrology outpatient clinic attendants of Cairo University Hospitals. We enrolled 68 semen samples divided into two groups: a study group (34 semen samples with bacteriospermia) and a control group (34 semen samples without bacteriospermia). The characteristics of the semen, including morphology, motility, count, liquefaction, viscosity, pH, volume, and appearance, were evaluated according to the standard protocols. Patients with and without bacteriospermia had a comparable liquefaction time ( p = .343), semen appearance and color ( p = 1.00), semen pH ( p = 1.00), velocity ( p = .163), and total sperm count ( p = .451). Patients with bacteriospermia were associated with lower progressive motility ( p = .001), nonprogressive motility ( p = .032), total motility ( p = .001), and normal forms ( p = .001). The prevalence of abnormal semen analysis was 64.71% in the study group compared with 35.29% in the control group. Staphylococcus aureus (67.6%) and Escherichia coli (14.7%) were the most commonly detected organisms. Samples from which Methicilin-resistant Staphylococcus aureus was isolated showed significant abnormalities in both progressive motility and normal morphology of sperm. Bacteriospermia has deteriorative effects on sperm quality parameters, such as semen volume, sperm motility, and sperm normal morphology.
Utilizing Experiential Learning Methods to Teach Substantive Law Courses to Undergraduate Students
Authors: Mahmood Anida , Hashim Haswira Nor Mohamad , Zakuan Zeti Zuryani Ahmad
Published: June 2023

This study proposes experiential learning methods for delivering and assessing substantive law courses to undergraduate students. The study reviews current experiential learning methods used to teach contract law, the most common substantive law course offered to law and non-law undergraduate students. The identified methods are synthesized and mapped to Kolb’s Experiential Learning Cycle. The study follows the PRISMA-ScR checklist and explanation guidelines to report its findings. A scholarly search was conducted on Google Scholar and four online databases (ACM Digital Library, EMERALD, PROQUEST and SCOPUS). Of the 44 studies that met the inclusion criteria, 141 essential original constructs were collected, and 7 methods were derived. The study found that role-plays and simulation methods recorded the highest percentage of original constructs (38%, n = 54), followed by fieldwork and clinical methods (26%, n = 36), case-based methods (11%, n = 15), writing task methods (9%, n = 12), problem-based learning methods (7%, n = 11), street law (5%, n = 7) and seminar-based methods (4%, n = 6). The study also synthesized 23 new items for experiential learning methods that may guide the teaching of substantive law courses to undergraduate students. This scoping review adds significant value to the current body of knowledge by presenting novel items that law academics can use to adopt experiential learning methods for teaching substantive law to undergraduate students. These items can also be adapted for the development of experiential-based learning course syllabi and assessments for other substantive law courses not included as a sample of analysis.
Abigail Geisinger Primary Care Scholars: An Innovative Educational Program Addressing Critical Workforce Needs
Authors: Scheinman Steven J , Adonizio Tanja , Schmude Michelle , Jeffries William , Hartle J Edward , Byerley Julie
Published: June 2023

The number of primary care physicians in the United States is inadequate to meet current or projected needs. This is likely exacerbated by continuing increases in the cost of medical education and student debt. The Geisinger Commonwealth School of Medicine is part of an integrated care delivery system in which primary care is central to managing health, improving access, and advancing value-based care. The need for primary care providers and psychiatrists is difficult to meet despite generous recruiting incentives. To address this, the Abigail Geisinger Scholars Program (AGSP) represents a novel curricular approach linked with the provision of full tuition and fees and a living stipend to students who commit to work at Geisinger in primary care or psychiatry following residency. The support is provided as a forgivable loan. The program features preferential clinical placements, curricular enhancements, and celebration of the dedicated cohort. Fair and nonpunitive provisions allow students to opt-out. The AGSP supports 45 students in each class of 115. Outcomes monitored include withdrawals from the AGSP; academic performance of participants and their satisfaction with the program; the number who choose to repay the loan rather than fulfill the service obligation; the percentage who remain at Geisinger and in primary care following the period of obligation; and other measures. This model offers an attractive opportunity for students to experience a curriculum enhanced in primary care while receiving generous financing for their medical education. It bolsters the primary care physician workforce and aligns care delivery with new financing models.
Changes in terpene biosynthesis and submergence tolerance in cotton
Authors: Sun Liangqing , Wang Junjuan , Cui Yupeng , Cui Ruifeng , Kang Ruiqing , Zhang Yuexin , Wang Shuai , Zhao Lanjie , Wang Delong , Lu Xuke , Fan Yapeng , Han Mingge , Chen Chao , Chen Xiugui , Guo Lixue , Ye Wuwei
Published: June 2023

Background

Flooding is among the most severe abiotic stresses in plant growth and development. The mechanism of submergence tolerance of cotton in response to submergence stress is unknown.

Results

The transcriptome results showed that a total of 6,893 differentially expressed genes (DEGs) were discovered under submergence stress. Gene Ontology (GO) enrichment analysis showed that DEGs were involved in various stress or stimulus responses. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that DEGs related to plant hormone signal transduction, starch and sucrose metabolism, glycolysis and the biosynthesis of secondary metabolites were regulated by submergence stress. Eight DEGs related to ethylene signaling and 3 ethylene synthesis genes were identified in the hormone signal transduction. For respiratory metabolism, alcohol dehydrogenase (ADH,GH_A02G0728) and pyruvate decarboxylase (PDC,GH_D09G1778) were significantly upregulated but 6-phosphofructokinase (PFK,GH_D05G0280), phosphoglycerate kinase (PGK,GH_A01G0945andGH_D01G0967) and sucrose synthase genes (SUS,GH_A06G0873andGH_D06G0851) were significantly downregulated in the submergence treatment. Terpene biosynthetic pathway-related genes in the secondary metabolites were regulated in submergence stress.

Conclusions

Regulation of terpene biosynthesis by respiratory metabolism may play a role in enhancing the tolerance of cotton to submergence under flooding. Our findings showed that the mevalonate pathway, which occurs in the cytoplasm of the terpenoid backbone biosynthesis pathway (ko00900), may be the main response to submergence stress.
Ability of the Analgesia Nociception Index variations to identify a response to a volume expansion of 250 mL of crystalloids in the operating room (REVANI): a prospective observational study
Authors: de Courson Hugues , Chadefaux Grégoire , Abel Benjamin , Georges Delphine , Verchere Eric , Biais Matthieu
Published: June 2023

Background

Analgesia Nociception Index (ANI) is a device based on analysis of the R-R interval and respiratory sinus arrhythmia to assess the balance between sympathetic and parasympathetic activity. The autonomic system is directly affected by load changes. Therefore, monitoring sympathetic tone and its change could theoretically allow tracking of load changes during volume expansion. The aim of the present study was to determine whether changes in ANI are able to track the increase in stroke volume caused by volume expansion (SV).

Methods

This prospective observational study included mechanically ventilated patients undergoing neurosurgery and benefiting from SV monitoring. Exclusion criteria were cardiac dysfunction, arrhythmias, beta-blockade therapy, and dysautonomia. SV was optimized by fluid administration of 250 ml of crystalloid fluid. A positive fluid increase was defined as a SV increase of 10% or more from baseline. Changes in SV and medium ANI (ANIm) were recorded before and 4 to 5 min after volume expansion.

Results

Sixty-nine patients had 104 fluid challenges (36 positive and 68 negative). Volume expansion resulted in a greater ANI increase in responders than in nonresponders. The change in ANIm > 5 predicted fluid responsiveness with a sensitivity of 68.4% (95% CI: 67.4% to 69.5%) and a specificity of 51.2% (95% CI: 50.1% to 52.3%). The area under the receiver operating characteristic curve was 0.546 (95% CI: 0.544 to 0.549) and appeared to be affected by remifentanil dose and baseline ANI.

Conclusion

Changes in ANIm induced by fluid challenge is not able to predict fluid responsiveness in mechanically ventilated patients undergoing neurosurgery.

Trial registration

Clinical trial registration: NCT04223414.
Free drug provision for tuberculosis increases patient follow-ups and successful treatment outcomes in the Indian private sector: a quasi experimental study using propensity score matching
Authors: Sodhi Ridhima , Penkunas Michael J. , Pal Arnab
Published: June 2023

Background

The private sector is an important yet underregulated component of the TB treatment infrastructure in India. The Joint Effort for Elimination of Tuberculosis (Project JEET) aims to link private sector TB care with the constellation of social support mechanisms available through the Indian National TB Elimination Programme (NTEP), including the provision of free fixed-dose combination (FDCs) drugs to patients. This quasi-experimental study analysed routinely collected data to determine the impact of free drugs on patient follow-ups and treatment outcomes.

Methods

We used data for private sector patients enrolled with Project JEET who were diagnosed with pulmonary and extrapulmonary TB between 1 January 2019 and 31 March 2020, and completed treatment by 31 December 2021. Propensity score matching was used to create a dataset to compare the number of follow-ups and proportion of successful treatment outcomes for patients on free drugs to a control group who paid out-of-pocket. 11,621 matched pairs were included in the analysis. Logistic regression and ordinary least squares regression models were used to estimate the impact of free drugs on number of follow-ups and treatment success, where latter is defined as treatment completion or cure.

Results

After controlling for potential confounders, patients on free drugs received on average 2.522 (95% C.I.: 2.325 to 2.719) additional follow-ups compared to patients who paid out of pocket. This equates to a 25% mean and 32% median increase in follow-ups for patients availing free drugs. For treatment success, patients receiving free drugs had 45% higher odds of a successful treatment (Odds Ratio: 1.452, 95% C.I.: 1.288 to 1.637).

Conclusions

Patients receiving free drugs were found to follow up with their treatment coordinator more frequently, in part likely to enable drug refilling, compared to patients who were paying out of pocket. These additional contacts would have offered opportunities to address concerns regarding side effects, provide additional treatment information, and connect with social support services, all of which subsequently contributed to patients’ continual engagement with their treatment. This potentially represents the unmeasured effect of free drugs on continual social support, which translates into a higher odds of treatment success for patients.
Mastectomy with Reconstruction Including Robotic Endoscopic Surgery (MARRES): a prospective cohort study of the Korea Robot-Endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG) and Korean Breast Cancer Study Group (KBCSG)
Authors: Ryu Jai Min , Lee Jeea , Lee Jeeyeon , Ko BeomSeok , Kim Joo Heung , Shin Hyukjai , Park Hyung Seok ,   Korea Robot-endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG)
Published: June 2023

Background

Robotic nipple-sparing mastectomy (RNSM) has emerged as a new treatment option for breast cancer and risk-reducing mastectomy (RRM) for women who have a high risk of pathogenic variants. Even though several studies have reported that RNSM is a feasible procedure, some argue that it should only be performed by specialized surgeons, and data on oncologic outcomes and patient-reported outcomes (PROs) are limited. Recently, the United States Food and Drug Administration and several surgeons warned that robotic breast surgery should be performed only by specialized surgeons and recommended that the benefits, risks, and alternatives of all available treatment options be discussed with patients so they can make informed treatment decisions. The Korea Robot-Endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG) has been established to evaluate, standardize, and teach this state-of-the-art procedure. We have designed a multicenter prospective cohort study entitled Mastectomy with Reconstruction Including Robot Endoscopic Surgery (MARRES) to report surgical, PRO, and oncologic outcomes.

Methods

MARRES is a multi-institution cohort study prospectively collecting data from patients undergoing mastectomy and reconstruction. The patient inclusion criteria are adult women older than 19 with breast cancer or a high risk of breast cancer (patients with BRCA1/2, TP53, PALB2 mutations, etc.), who have scheduled therapeutic or RRM and want immediate reconstruction. Surgical outcomes, including pre- and postoperative photos, oncologic outcomes, cost-effectiveness, and PRO, are collected. The primary endpoints are postoperative complication rates within 30 postoperative days and the Clavien-Dindo grade of postoperative complications within 180 postoperative days. The secondary endpoints are 5-year postoperative recurrence-free survival and cancer incidence rate (for those who underwent RRM), patient satisfaction with reconstruction expectations preoperative (baseline) and results within 6 to 12 postoperative months, surgeon satisfaction with postoperative results in 6 postoperative months, and cost-effectiveness of the definitive surgery. Patient recruitment will be completed in April 2025, and the target number of enrolled patients is 2000.

Discussion

This study will provide evidence about the surgical outcomes, oncologic outcomes, and patient satisfaction with RNSM and endoscopic nipple-sparing mastectomy (NSM), compared with conventional NSM.

Trial registration

ClinicalTrials.gov Identifier NCT04585074. Registered April 8, 2020.
Delphi panel to obtain clinical consensus about using long-acting injectable antipsychotics to treat first-episode and early-phase schizophrenia: treatment goals and approaches to functional recovery
Authors: Arango Celso , Fagiolini Andrea , Gorwood Philip , Kane John M. , Diaz-Mendoza Sergio , Sahota Navdeep , Correll Christoph U.
Published: June 2023

Background

Schizophrenia is mostly a chronic disorder whose symptoms include psychosis, negative symptoms and cognitive dysfunction. Poor adherence is common and related relapse can impair outcomes. Long-acting injectable antipsychotics (LAIs) may promote treatment adherence and decrease the likelihood of relapse and rehospitalization. Using LAIs in first-episode psychosis (FEP) and early-phase (EP) schizophrenia patients could benefit them, yet LAIs have traditionally been reserved for chronic patients.

Methods

A three-step modified Delphi panel process was used to obtain expert consensus on using LAIs with FEP and EP schizophrenia patients. A literature review and input from a steering committee of five experts in psychiatry were used to develop statements about patient population, adverse event management, and functional recovery. Recruited Delphi process psychiatrists rated the extent of their agreement with the statements over three rounds (Round 1: paper survey, 1:1 interview; Rounds 2–3: email survey). Analysis rules determined whether a statement progressed to the next round and the level of agreement deemed consensus. Measures of central tendency (mode, mean) and variability (interquartile range) were reported back to help panelists assess their previous responses in the context of those of the overall group.

Results

The Delphi panelists were 17 psychiatrists experienced in treating schizophrenia with LAIs, practicing in seven countries (France, Italy, US, Germany, Spain, Denmark, UK). Panelists were presented with 73 statements spanning three categories: patient population; medication dosage, management, and adverse events; and functional recovery domains and assessment. Fifty-five statements achieved ≥ 80% agreement (considered consensus). Statements with low agreement (40-79%) or very low agreement (< 39%) concerned initiating dosage in FEP and EP patients, and managing loss of efficacy and breakthrough episodes, reflecting current evidence gaps. The panel emphasized benefits of LAIs in FEP and EP patients, with consensus that LAIs can decrease the risk of relapse, rehospitalization, and functional dysfunction. The panel supported links between these benefits and multidimensional longer-term functional recovery beyond symptomatic remission.

Conclusions

Findings from this Delphi panel support the use of LAIs in FEP and EP schizophrenia patients regardless of disease severity, number of relapses, or social support status. Gaps in clinician knowledge make generating evidence on using LAIs in FEP and EP patients critical.
An economic evaluation of two PCR-based respiratory panel assays for patients admitted to hospital with community-acquired pneumonia (CAP) in the UK, France and Spain
Authors: Miners Lisa , Huntington Susie , Lee Nathaniel , Turner Katy M. E. , Adams Elisabeth
Published: June 2023

Background

On admission to hospital, patients with community-acquired pneumonia (CAP), undergo extensive diagnostic testing. Two high-throughput laboratory-based PCR panels which return a result in 5.5 hours (h) have been developed to test for pathogens commonly associated with upper (Respiratory 1 Panel) and lower (Respiratory 3 Panel) respiratory tract infections (GeneFirst, Oxford). These could replace multiple diagnostic tests currently used.

Methods

An online survey, completed by senior clinicians in the UK, France and Spain, was used to collect data on the diagnostic testing of immunocompetent and immunocompromised adults admitted to hospital with CAP, including the cost of diagnostics. Data were used to inform a cost-comparison model. For each country, the average cost of diagnostic testing per patient was calculated separately for immunocompetent and immunocompromised patients.

The model compared three testing strategies with standard of care (SoC). In the Panel 1 strategy, the Respiratory 1 Panel was used for patients that would otherwise have tests which could be replaced by Respiratory 1 Panel, equivalent strategies for Respiratory 3 Panel and for both panels combined were assessed.

Results

In total, 48 surveys were completed (UK = 17; France = 15; Spain = 16). Compared with SoC, the Panel 1 + 3 strategy was most favourable, resulting in cost savings for immunocompetent and immunocompromised patients respectively, of €22.09 (£18.50) and €26.12 (£21.88) in the UK, €99.60 and €108.77 in France and €27.07 and €51.87 in Spain.

Conclusion

In all three countries, the use of these respiratory panels could reduce the average cost of diagnostics used for patients admitted to hospital with CAP.
Can home care work be organized to promote health among the workers while maintaining productivity? An investigation into stakeholders’ perspectives on organizational work redesign concepts based on the Goldilocks Work principles
Authors: Liaset Ingeborg Frostad , Fimland Marius Steiro , Holtermann Andreas , Mathiassen Svend Erik , Redzovic Skender
Published: June 2023

Background

Due to the aging population, the need for home care services is increasing in most Western countries, including Norway. However, the highly physical nature of this job could contribute to make recruiting and retaining qualified home care workers (HCWs) challenging. This issue may be overcome by adopting the Goldilocks Work principles, aiming at promoting workers’ physical health by determining a “just right” balance between work demands and recovery periods while maintaining productivity. The aim of this study was to 1) gather suggestions from home care employees on suitable organizational (re)design concepts for promoting HCWs’ physical health and 2) have researchers and managers define actionable behavioral aims for the HCWs for each proposed (re)design concept and evaluate them in the context of the Goldilocks Work principles.

Methods

HCWs, safety representatives, and operation coordinators (n = 14) from three Norwegian home care units participated in digital workshops led by a researcher. They suggested, ranked, and discussed redesign concepts aimed at promoting HCWs’ health. The redesign concepts were subsequently operationalized and evaluated by three researchers and three home care managers.

Results

Workshop participants suggested five redesign concepts, namely "operation coordinators should distribute work lists with different occupational physical activity demands more evenly between HCWs", "operation coordinators should distribute transportation modes more evenly between HCWs", "Managers should facilitate correct use of ergonomic aids and techniques", "HCWs should use the stairs instead of the elevator", and "HCWs should participate in home-based exercise training with clients". Only the first two redesign concepts were considered to be aligned with the Goldilocks Work principles. A corresponding behavioral aim for a “just right” workload was defined: reduce inter-individual differences in occupational physical activity throughout a work week.

Conclusions

Operation coordinators could have a key role in health-promoting organizational work redesign based on the Goldilocks Work principles in home care. By reducing the inter-individual differences in occupational physical activity throughout a work week, HCWs’ health may be improved, thus reducing absenteeism and increasing the sustainability of home care services. The two suggested redesign concepts should be considered areas for evaluation and adoption in practice by researchers and home care services in similar settings.
Generation, evolution, interfering factors, applications, and challenges of patient-derived xenograft models in immunodeficient mice
Authors: Zeng Mingtang , Ruan Zijing , Tang Jiaxi , Liu Maozhu , Hu Chengji , Fan Ping , Dai Xinhua
Published: June 2023

Establishing appropriate preclinical models is essential for cancer research. Evidence suggests that cancer is a highly heterogeneous disease. This follows the growing use of cancer models in cancer research to avoid these differences between xenograft tumor models and patient tumors. In recent years, a patient-derived xenograft (PDX) tumor model has been actively generated and applied, which preserves both cell–cell interactions and the microenvironment of tumors by directly transplanting cancer tissue from tumors into immunodeficient mice. In addition to this, the advent of alternative hosts, such as zebrafish hosts, or in vitro models (organoids and microfluidics), has also facilitated the advancement of cancer research. However, they still have a long way to go before they become reliable models. The development of immunodeficient mice has enabled PDX to become more mature and radiate new vitality. As one of the most reliable and standard preclinical models, the PDX model in immunodeficient mice (PDX-IM) exerts important effects in drug screening, biomarker development, personalized medicine, co-clinical trials, and immunotherapy. Here, we focus on the development procedures and application of PDX-IM in detail, summarize the implications that the evolution of immunodeficient mice has brought to PDX-IM, and cover the key issues in developing PDX-IM in preclinical studies.
Nanostructures for prevention, diagnosis, and treatment of viral respiratory infections: from influenza virus to SARS-CoV-2 variants
Authors: Sharifi Esmaeel , Yousefiasl Satar , Trovato Maria , Sartorius Rossella , Esmaeili Yasaman , Goodarzi Hamid , Ghomi Matineh , Bigham Ashkan , Moghaddam Farnaz Dabbagh , Heidarifard Maryam , Pourmotabed Samiramis , Nazarzadeh Zare Ehsan , Paiva-Santos Ana Cláudia , Rabiee Navid , Wang Xiangdong , Tay Franklin R.
Published: June 2023

Viruses are a major cause of mortality and socio-economic downfall despite the plethora of biopharmaceuticals designed for their eradication. Conventional antiviral therapies are often ineffective. Live-attenuated vaccines can pose a safety risk due to the possibility of pathogen reversion, whereas inactivated viral vaccines and subunit vaccines do not generate robust and sustained immune responses. Recent studies have demonstrated the potential of strategies that combine nanotechnology concepts with the diagnosis, prevention, and treatment of viral infectious diseases. The present review provides a comprehensive introduction to the different strains of viruses involved in respiratory diseases and presents an overview of recent advances in the diagnosis and treatment of viral infections based on nanotechnology concepts and applications. Discussions in diagnostic/therapeutic nanotechnology-based approaches will be focused on H1N1 influenza, respiratory syncytial virus, human parainfluenza virus type 3 infections, as well as COVID-19 infections caused by the SARS-CoV-2 virus Delta variant and new emerging Omicron variant.

Graphical Abstract
HIF1α-dependent hypoxia response in myeloid cells requires IRE1α
Authors: Mawambo Gaëlle , Oubaha Malika , Ichiyama Yusuke , Blot Guillaume , Crespo-Garcia Sergio , Dejda Agnieszka , Binet François , Diaz-Marin Roberto , Sawchyn Christina , Sergeev Mikhail , Juneau Rachel , Kaufman Randal J. , Affar El Bachir , Mallette Frédérick A. , Wilson Ariel M. , Sapieha Przemyslaw
Published: June 2023

Cellular adaptation to low oxygen tension triggers primitive pathways that ensure proper cell function. Conditions of hypoxia and low glucose are characteristic of injured tissues and hence successive waves of inflammatory cells must be suited to function under low oxygen tension and metabolic stress. While Hypoxia-Inducible Factor (HIF)-1α has been shown to be essential for the inflammatory response of myeloid cells by regulating the metabolic switch to glycolysis, less is known about how HIF1α is triggered in inflammation. Here, we demonstrate that cells of the innate immune system require activity of the inositol-requiring enzyme 1α (IRE1α/XBP1) axis in order to initiate HIF1α-dependent production of cytokines such as IL1β, IL6 and VEGF-A. Knockout of either HIF1α or IRE1α in myeloid cells ameliorates vascular phenotypes in a model of retinal pathological angiogenesis driven by sterile inflammation. Thus, pathways associated with ER stress, in partnership with HIF1α, may co-regulate immune adaptation to low oxygen.
MiR-137 promotes TLR4/NF-κB pathway activity through targeting KDM4A, inhibits osteogenic differentiation of human bone marrow mesenchymal stem cells and aggravates osteoporosis
Authors: Yu Ying-feng , Yao Pei-quan , Wang Zhi-kun , Xie Wen-wei
Published: June 2023

Purpose

As the global population ages rapidly, osteoporotic fractures have become an important public health problem. Previous studies have suggested that miR-137 is involved in the regulation of bone formation, but its specific regulatory mechanism remains unclear. In this study, we aimed to explore the expression, role, and regulatory mechanism of miR-137 in the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs).

Methods

hBMSCs were induced into osteoblasts at first, and the expression level of miR-137 at different time points was detected. After knockdown and overexpression of miR-137, the effect of miR-137 on the osteogenic differentiation of hBMSCs was examined through alkaline phosphatase (ALP) staining and Alizarin Red staining. Western blotting was performed to detect the expression of runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway. Bioinformatics websites were used to predict the target binding sites for miR-137 and KDM4A, and the results were validated using luciferase reporter gene experiments. Moreover, the ALP activity, calcium nodule formation, and activation of Runx2, OCN, and TLR4/NF-κB pathways were observed after knockdown of KDM4A.

Results

The expression of miR-137 decreased during osteogenic differentiation. Knockdown of miR-137 expression increased the osteogenic ability of hBMSCs, while overexpression of it weakened the ability. Through the activation of the TLR4/NF-κB pathway, miR-137 inhibited osteogenic differentiation. KDM4A was identified as a predicted target gene of miR-137. After knocking down KDM4A expression, the osteogenic ability of hBMSCs was diminished, and the TLR4/NF-κB pathway was activated. Furthermore, the osteogenic ability of hBMSCs was partially restored and the activation level of TLR4/NF-κB was reduced after miR-137 knockdown.

Conclusion

MiR-137 enhances the activity of the TLR4/NF-κB pathway by targeting KDM4A, thereby inhibiting the osteogenic differentiation of hBMSCs and exacerbating osteoporosis.
Comparison of clinical outcome of lumbar spinal stenosis surgery in patients with and without osteoporosis: a prospective cohort study
Authors: Aghajanloo Mashhood , Abdoli Ali , Poorolajal Jalal , Abdolmaleki Sajjad
Published: June 2023

Background

Osteoporosis is one of the most important risk factors for failure of the spine instrumentation. Management of patients with osteoporosis who requires spinal surgery because of the difficulty in instrument placement and the potential complications is still a challenge. This study was designed to evaluate the clinical outcome of lumbar spinal canal stenosis after instrumentation in patients with and without osteoporosis.

Methods

This prospective cohort study was performed from June 2018 to December 2020, in Be'sat Hospital, Hamadan, Iran. The sample consisted of patients over 50 years old referred to Be'sat Hospital with a diagnosis of lumbar spinal canal stenosis who underwent instrumental surgery (n = 107). Based on bone densitometry, the sample was divided into two groups with osteoporosis (n = 34) and without osteoporosis (n = 73). To collect data, we used a three-part researcher-made questionnaire (demographic information, medical records information, and paraclinical parameters). Statistical analyzes were performed by the Fisher Exact, chi-square, independent t-test, Multiple ANCOVA, Mann–Whitney and the Rank Wilcoxson tests using Stata version 17 software.

Results

The mean age (SD) of patients in the two groups with and without osteoporosis was 67.9 (7.0) and 59.1 (5.1) years, respectively (p = 0.001). The results indicated that a significant difference was observed between the two groups in sex (p = 0.032), educational status (p = 0.001), marital status (p = 0.023), employment status (p = 0.004), menopausal status (p = 0.018), taking corticosteroids (p = 0.028), and body mass index (p = 0.015). Also, there was a significant difference between two groups in the loosening of instrument (p = 0.039), the postoperative pain intensity (p = 0.007), fusion (p = 0.047), and neurogenic claudication (p = 0.003). Based on multiple ANCOVA test, there was not a significant difference between two groups in the clinical and paraclinical charatecristics (p > 0.05). The mean (SD) of T-Score in the osteoporosis group was 3.06 (0.37).

Conclusion

This study provides evidence that there is no significant difference in the clinical outcomes of lumbar spine instrumentation due to spinal canal stenosis in patients with and without osteoporosis. Because of the high cost of specific instrumentation developed for patients with osteoporosis and their unavailability, it seems that the use of conventional instrumentation along with complete treatment of osteoporosis can help improve the clinical outcome of surgery in these patients.
BCAT1 controls embryonic neural stem cells proliferation and differentiation in the upper layer neurons
Authors: Zhang Shukui , Zhao Jinyue , Zhao Cheng , Su Libo , Jiao Jianwei
Published: June 2023

The regulation of neural stem cell (NSC) proliferation and differentiation during brain development is a precisely controlled process, with the production of different neuronal subtypes governed by strict timelines. Glutamate is predominantly used as a neurotransmitter by the subtypes of neurons in the various layers of the cerebral cortex. The expression pattern of BCAT1, a gene involved in glutamate metabolism, in the different layers of neurons has yet to be fully understood. Using single-cell data, we have identified seven different states of NSCs and found that state 4 is closely associated with the development of projection neurons. By inferring the developmental trajectory of different neuronal subtypes from NSC subsets of this state, we discovered that BCAT1 is involved in the regulation of NSC proliferation and differentiation and is specifically highly expressed in layer II/III and IV neurons. Suppression of BCAT1 through shRNA resulted in a reduction in NSC proliferation and an abnormal development of layer II/III and IV neurons. These findings provide new insights into the role of BCAT1 in the regulation of NSC behavior and neuronal development.