Improved motif-scaffolding with SE(3) flow matching.

Protein design often begins with knowledge of a desired function from a motif which motif-scaffolding aims to construct a functional protein around. Recently, generative models have achieved breakthrough success in designing scaffolds for a diverse range of motifs. However, the generated scaffolds tend to lack structural diversity, which can hinder success in wet-lab validation. In this work, we extend FrameFlow, an SE(3) flow matching model for protein backbone generation, to perform motif-scaffolding with two complementary approaches. The first is motif amortization, in which FrameFlow is trained with the motif as input using a data augmentation strategy. The second is motif guidance, which performs scaffolding using an estimate of the conditional score from FrameFlow, and requires no additional training. Both approaches achieve an equivalent or higher success rate than previous state-of-the-art methods, with 2.5 times more structurally diverse scaffolds. Code: https://github.com/microsoft/frame-flow.

Association between frailty status and complications in patients undergoing surgical excision of malignant esophageal neoplasms.

Background: Research within the last decade highlights the patients' frailty status as an important predictor of esophageal cancer outcomes, but the literature evaluating frailty's role in these patients remains limited. We evaluated the role of frailty in patients undergoing resection of malignant esophageal neoplasms. Methods: We used the Nationwide Readmissions Database from 2016 and 2017 to identify patients who underwent excision of a malignant esophageal neoplasm. Patient frailty was queried using the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnosis indicator. Propensity score matching identified 289 frail patients and 281 non-frail patients. Mann-Whitney U testing was performed and receiver operating characteristic (ROC) curves were created, following the creation of logistic regression models for predicting discharge disposition. The area under the curve (AUC) served as a proxy for model performance. Results: Frail patients had significantly more nonroutine discharges, longer inpatient lengths of stay, higher costs, more acute infections, posthemorrhagic anemia and deep vein thrombosis, and greater mortality (P<0.05). No significant differences were found between the 2 cohorts with respect to readmission rates, pulmonary embolism or dysphagia. Predictive models for patient discharge disposition demonstrated that frailty status in combination with age resulted in better ROC curves (AUC: 0.652) compared to models using age alone (AUC: 0.601). Conclusions: Frailty was found to be significantly correlated with higher rates of inpatient medical complications following esophagectomy. The inclusion of patient frailty status in predictive models for discharge disposition resulted in a better predictive capacity compared to those using age alone.

Impact of Bacteria Types on the Clinical Outcomes of Spontaneous Bacterial Peritonitis.

BACKGROUND AND AIMS: Cirrhotic patients presenting with spontaneous bacterial peritonitis (SBP) have elevated risk of short-term mortality. While high Model for End-Stage Liver Disease-Sodium score (MELD-Na) and ascites culture yielding multi-drug resistance (MDR) bacteria are well established risk factors for further aggravating mortality, the impact of individual, causative microorganisms and their respective pathogenesis have not been previously investigated. METHODS: This is a retrospective study of 267 cirrhotic patients at two tertiary care hospitals undergoing paracentesis from January 2015 to January 2021 who presented with ascitic PMN count > 250 cells/mm3. The primary outcome was SBP progression defined as death or liver transplantation within 1-month of paracentesis stratified by microorganism type. RESULTS: Of 267 patients with SBP, the ascitic culture yielded causative microorganism in 88 cases [median age 57 years (IQR 52-64)]; 68% male; median MELD-Na 29 (IQR 23-35). The microbes isolated were E. coli (33%), Streptococcus (15%), Klebsiella (13%), Enterococcus (13%), Staphylococcus (9%) and others (18%); 41% were MDR. Cumulative incidence of SBP progression within 1-month was 91% (95% CI 67-100) for Klebsiella, 59% (95% CI 42-76) for E. coli, and 16% (95% CI 4-51) for Streptococcus. After adjusting for MELD-Na and MDR, risk of SBP progression remained elevated for Klebsiella (HR 2.07; 95% CI 0.98-4.24; p-value = 0.06) and decreased for Streptococcus (HR 0.28; 95% CI 0.06-1.21; p-value = 0.09) compared to all other bacteria. CONCLUSION: Our study found Klebsiella-associated SBP had worse clinical outcomes while Streptococcus-associated SBP had the most favorable outcomes after accounting for MDR and MELD-Na. Thus, identification of the causative microorganism is crucial not only for optimizing the treatment but for prognostication.

When Health Intersects with Gender and Sexual Diversity: Medical Students' Attitudes Towards LGBTQ Patients.

A central tenet of the health professions is that of equitable access to health care. However, disparities in equitable healthcare provision continues to be a challenge in many societies due to prejudices against the LGBTQ community. This study was aimed at exploring the attitudes of medical students toward LGBTQ patients in Malaysia. A qualitative approach was adopted to seek depth of understanding of clinical year medical students' perceptions and attitudes toward LGBTQ patients. Data were collected in 2018 through individual interviews and focus group discussions with a total of 29 participants, using a semi-structured question guideline. Purposive sampling comprised representation from the three major ethnic groups in Malaysia. Thematic analysis using NVivo highlighted three main themes i.e., neutrality, in compliance with the Professional Code of Conduct; implicit biases and tolerance of an Odd Identity; explicit biases with prejudices and stereotyping. The lack of knowledge and understanding of the nature and issues of sexuality is problematic as found in this study. They are primarily biases and prejudices projected onto marginalized LGBTQ patients who must contend with multiple jeopardies in conservative societies such as in Malaysia. With some state policies framed around Islam the concern is with the belief among Malay/Islamic students for LGBTQ individuals to go through conversion 'therapies' to become cisgender and heterosexual.

Comprehensive meta-analysis of randomized controlled trials of Lactated Ringer's versus Normal Saline for acute pancreatitis.

INTRODUCTION: Fluid resuscitation is the keystone of treatment for acute pancreatitis. Though clinical guidelines and expert opinions agree on large volume resuscitation, debate remains on the optimal fluid type. The most commonly used fluids are Lactated Ringer's (LR) and Normal Saline (NS), but the studies published to date comparing LR vs NS yield conflicting results. We aimed to identify and quantitatively synthesize existing high quality data of the topic of fluid type or acute pancreatitis resuscitation. METHODS: In collaboration with the study team, an information specialist performed a comprehensive literature review to identify reports addressing type of fluid resuscitation. Studies were screened using the Covidence system by two independent reviewers in order to identify Randomized controlled trials comparing LR versus NS. The main outcome was the development of moderately severe or severe pancreatitis and additional outcomes included local complications, ICU admission, and length of stay. Pooled odds ratios were estimated using the random effects model and standardized mean difference to compare continuous variables. RESULTS: We reviewed 7964 abstracts and 57 full text documents. Four randomized controlled trials were identified and included in our meta-analyses. There were a total of 122 patients resuscitated with LR versus 126 with NS. Patients resuscitated with LR were less likely to develop moderately severe/severe pancreatitis (OR 0.49; 95 % CI 0.25-0.97). There was no difference in development of SIRS at 24 or 48 h or development of organ failure between the two groups. Patients resuscitated with LR were less likely to require ICU admission (OR 0.33; 95 % CI 0.13-0.81) and local complications (OR 0.42; 95 % CI 0.2-0.88). While there was a trend towards shorter hospitalizations for LR (SMD -0.18, 99 % CI -0.44-0.07), it was not statistically significant. CONCLUSION: Resuscitation with LR reduces the development of moderately severe-severe pancreatitis relative to NS. Nevertheless, no difference in SIRS development or organ failure underscores the need for further studies to verify this finding and define its mechanism.

Mental Health of Refugee Children: A Discursive Look at Causes, Considerations and Interventions.

There is a growing need both locally and internationally to manage the effects of traumatic and loss experiences on the development and recovery of refugee children and young people. Trauma, whether active or through deprivation, is degenerative, with crucial impact on developing bodies, brains and minds. This discursive article considers the nature and scope of the problem and draws on literature and current frameworks to suggest the importance of interventions and proactive protection of mental health for this sub-group of refugees. School is discussed as a place of primary intervention but also a player in creative and sophisticated multimodal integrative services. A range of approaches can be, and, indeed are used in response to mental health issues for children in detention or upon resettlement. Schooling represents one such solution, providing a multi-pronged approach to facilitate mental health improvement for these children. For children needing to recover from loss and trauma secondary to experiences as a refugee, school offers a developmentally appropriate space to mobilise and enhance recovery, both at a simple level and as part of more specialised secondary and tertiary level care. The implications for future practice among health care professionals is to understand the mental health plight of refugee children, through both their pre-arrival exposure to trauma and their post-arrival, detention setting, the key role that schooling can play in facilitating mental health, and the capacity to advocate for programmes and services to work collaboratively with schools to achieve greater access for refugee children.

Pre-tertiary education, ethnicity, and attitudes of Asian medical undergraduates towards communication skills.

OBJECTIVES: This study was aimed at determining whether the pre-tertiary education system and ethnicity have any association with the attitudes of medical undergraduates towards communication skills. It also sought to determine if attitudes should have any relationship with communication skills assessment outcomes. METHODS: A cross-section survey design was performed with 323 participants from two cohorts of medical undergraduates, i.e., first-year (n = 153) and second-year students (n = 170) who completed the Communication Skills Attitude Scale. Participants comprised of the main ethnic groups in Malaysia, i.e., Malays, Chinese and Indians, from different language medium pre-tertiary education backgrounds. Attitude measurements were compared with OSCE outcomes. RESULTS: There was a significant difference in Negative Attitude Scale between pre-tertiary education system with attitudes towards communication skills (F (3, 319) = 7.79, p = .001), but no significant difference with Positive Attitude Scale (F (3, 319) = 0.43, p = .649). There was no significant difference between ethnicity and attitudes towards communication skills with PAS (F (2, 320) = 0.66, p = .519) and NAS (F (2, 320) = 1.24, p = .291). Students from Chinese medium education system had stronger negative attitudes with a mean score of 14.7 (n = 56, SD = 3.6) for primary school levels and 15.9 (n = 17, SD = 3.0) for secondary school levels, compared with others. There was no significant prediction of student's attitudes towards assessments outcomes. CONCLUSIONS: Preliminary findings from the small data pool suggest indicative relationships requiring further studies with more participants and proportionate pre-tertiary education system backgrounds.

Providing a Safe Environment in a Psychiatric Ward: Nurses and Vigilance in Iran.

The aim of this study was to explore nurses' use of vigilance in the provision of inpatient psychiatric care. In this qualitative exploratory descriptive design study, 16 nurses working in inpatient psychiatric units were recruited through purposive sampling. Data were collected by semi-structured interviews and fieldwork observations and analysed using conventional content analysis. According to participants, nurses' vigilance is related to synthesising knowledge, experience, communication, and presence. This conclusion was derived from four main themes: understanding the context of the psychiatric ward; continuous monitoring; cognitive assessments; and involving others. The study highlights the significance of education for all mental health staff and provision of appropriate information to all patients and their companions about psychiatric disorders and the side effects of prescribed medications. Of importance is the skill of active listening to the concerns of patients and the demonstration of commitment by nurses to follow-up on reports from stakeholders. Imparting the skills and experiences of senior nurses to novice nurses and their presence alongside other nurses on work-shifts can be effective in promoting vigilance.

Therapeutic Relationships and Safety of Care in Iranian Psychiatric Inpatient Units.

Enhancing therapeutic relationships between patients and staff is of central importance to improve the quality and safety of care in psychiatric inpatient units. However, there is limited evidence as to how therapeutic relationships may be enabled in this specific context. This paper presents findings of a study that explored the link between therapeutic relationships and safety in Iranian psychiatric inpatient units. In this exploratory, descriptive study, seven patients at the point of discharge and 19 staff in psychiatric inpatient units in Iran were interviewed regarding their experiences of care. The quality of staff-patient relationship in providing a safe environment was categorized into two groups of "facilitators" and "inhibitors". Facilitators of a safe environment included "supportive relationship with patients" and "improving patient capacity for self-efficacy/self-control". Inhibitors, on the other hand, included "detachment from patients" and "domination over patients", which ultimately limited safety on the ward. Findings indicate interrelated environmental, patient and staff factors mediating the potential for therapeutic relationships and quality and safety of care. Findings suggest the need for more effective preparation and support for staff working within psychiatric inpatient settings. In addition, environments more conducive to collaborative recovery-oriented practice are required to enhance therapeutic relationships and improve quality and safety of care. Both individual staff responsibility and effective leadership are required to realize change.

Identifying HIV/AIDS primary care development needs.

AIM: This paper reports a study aimed at identifying the primary health care experiences of people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) in Malaysia. The rationale behind the study was to enable informed action for developing more responsive and effective primary care. BACKGROUND: Reports such as from the World Health Organisation forecast sharp escalations in the incidence of HIV/AIDS in Malaysia and the Asia-Pacific region within the next few years. With sparse information on the course of infection on the local population and an understanding of health care needs of those afflicted, health services would be ill-prepared for projected increases. METHOD: Semi-structured interviews were conducted with a convenience sample of 99 patients attending two major HIV/AIDS clinics in Malaysia. FINDINGS: Several gaps in care provision were highlighted, such as with treatment/consultation facilities and availability and accessibility of information. What is also evident is that there are a number of good support services available but not well publicized to those in need of them. That includes health professionals who could be making appropriate referrals. The lack of communications and inter-professional working appears to be part of the problem. CONCLUSION: The findings provide baseline data and preliminary insights to government and other service providers towards advancing, optimizing and refining existing policies and infrastructure. Although the availability of a number of primary care facilities have been identified, the study indicates the need for more effective co-ordinated efforts with clear leadership to pull together scarce resources towards the aim of some degree of seamless primary care provision. It is suggested that nurses would be well placed for such a role in view of the nature of their education and training that helps prepare them for the multi-faceted role.

Socio-cultural perspectives on the image of nursing: the Hong Kong dimension.

Socio-cultural perspectives on the image of nursing: The Hong Kong dimension¶Using structured interviews a study was undertaken with 19 high school students in Hong Kong to elicit their perceptions of nursing as a profession. The study also sought to gauge the extent of the students' intentions on pursuing a career in nursing. Responses were content analysed to determine the extent of knowledge and understanding held, intentions on choosing nursing as a career and their reasons. Findings suggest the image of nursing to be poor and that nursing as a career is far from desirable amongst the teenagers of Hong Kong. The reasons appear to be related to the notion of monetary rewards and status within the Hong Kong community. There is also a lack of knowledge as to what nurses do. The implications of such findings include the lost potential for recruitment of candidates of high calibre with a lot to offer the profession and their society. It suggests the need for the profession to find ways of publicizing and marketing the positive aspects with elements of realism which the general population in that part of the world could relate to more readily.