bluuebunny/crossref_metadata_2025 huggingface dataset:
Geospatial Analysis of Malaria Burden in Kagera Region, Northwestern Tanzania Using Health Facility and Community Survey Data
Authors: Petro Daniel A , Shaban Nyimvua , Aaron Sijenunu , Chacky Frank , Lazaro Samuel , Boni Maciej F , Ishengoma Deus S
Published: October 2024

Background

Malaria transmission in Tanzania has declined significantly over the last 2 decades due to scaled-up control interventions. However, recent confirmation of artemisinin partial resistance (ART-R) in Kagera region in northwest Tanzania threatens the ongoing efforts to eliminate malaria in the country. This study was conducted according to the World Health Organization recommendation to generate evidence of malaria burden in areas with confirmed ART-R as the first step before developing a response strategy to the resistance.

Methods

We assessed the local burden of malaria in Kagera region by geospatial analysis, using data collected retrospectively from health facilities and community surveys from 2015 to 2023 to identify malaria hot spots.

Results

From 2017 to 2023, a total of 8 124 363 suspected malaria cases were reported by health facilities, and 2 983 717 (36.7% [95% range across wards, 22.7%–50.7%]) tested positive by rapid diagnostic tests. Test positivity rates were similar among patients aged <5 years (33.1% [95% range, 19.7%–46.5%]) and those aged ≥5 years (33.7% [21.0%–46.5%]). The malaria prevalence was 10.0% (95% range across wards, 5.1%–14.9% [n = 84 999 of 853 761]) in pregnant women and 26.1% (11.7%–40.6% [n = 3409 of 13 065]) in schoolchildren. Despite high temporal variations, we identified hot spots and cold spots, including persistently high burden in 69 of 192 wards (35.9%).

Conclusions

The malaria burden in Kagera exhibited high temporal and spatial heterogeneity, with schoolchildren showing the highest prevalence. This demographic pattern underlines the need for targeted interventions and provides evidence for developing an ART-R response for the region.
Successful Treatment of Recurrent Extensively Drug-Resistant Elizabethkingia anophelis Bacteremia Secondary to Ventricular Assist Device–Associated Infection
Authors: Vessely Madeleine B , Siddiqui Marrium , Kling Kendall , Guenette Alexis , Bachta Kelly E R
Published: October 2024

Elizabethkingia anophelis is an emerging pathogen increasingly implicated in health care–associated infections. Here, we report a case of recurrent ventricular assist device–associated infection caused by multidrug-resistant Elizabethkingia anophelis and describe the clinical course, treatment challenges, and ultimate case resolution. Our results demonstrate that standard clinical methodologies for determining trimethoprim-sulfamethoxazole minimum inhibitory concentration, including VITEK2 and gradient diffusion tests, may be unsuitable for Elizabethkingia anophelis as they result in false-negative susceptibility results. The discrepancy between antimicrobial susceptibility testing reported here highlights the importance of investigating and validating the applicability of standard clinical antimicrobial susceptibility testing and interpretation when treating emerging pathogens such as Elizabethkingia anophelis.
Modeling human activity comprehension at human scale: Prediction, segmentation, and categorization
Authors: Nguyen Tan T , Bezdek Matthew A , Gershman Samuel J , Bobick Aaron F , Braver Todd S , Zacks Jeffrey M
Published: October 2024

Humans form sequences of event models—representations of the current situation—to predict how activity will unfold. Multiple mechanisms have been proposed for how the cognitive system determines when to segment the stream of behavior and switch from one active event model to another. Here, we constructed a computational model that learns knowledge about event classes (event schemas), by combining recurrent neural networks for short-term dynamics with Bayesian inference over event classes for event-to-event transitions. This architecture represents event schemas and uses them to construct a series of event models. This architecture was trained on one pass through 18 h of naturalistic human activities. Another 3.5 h of activities were used to test each variant for agreement with human segmentation and categorization. The architecture was able to learn to predict human activity, and it developed segmentation and categorization approaching human-like performance. We then compared two variants of this architecture designed to better emulate human event segmentation: one transitioned when the active event model produced high uncertainty in its prediction and the other transitioned when the active event model produced a large prediction error. The two variants learned to segment and categorize events, and the prediction uncertainty variant provided a somewhat closer match to human segmentation and categorization—despite being given no feedback about segmentation or categorization. These results suggest that event model transitioning based on prediction uncertainty or prediction error can reproduce two important features of human event comprehension.
BOWIE-ALIGN: A JWST comparative survey of aligned versus misaligned hot Jupiters to test the dependence of atmospheric composition on migration history
Authors: Kirk James , Ahrer Eva-Maria , Penzlin Anna B T , Owen James E , Booth Richard A , Alderson Lili , Christie Duncan A , Claringbold Alastair B , Esparza-Borges Emma , Fisher Chloe E , López-Morales Mercedes , Mayne N J , McCormack Mason , Meech Annabella , Panwar Vatsal , Powell Diana , Sergeev Denis E , Taylor Jake , Tsai Shang-Min , Valentine Daniel , Wakeford Hannah R , Wheatley Peter J , Zamyatina Maria
Published: October 2024

A primary objective of exoplanet atmosphere characterization is to learn about planet formation and evolution, however, this is challenged by degeneracies. To determine whether differences in atmospheric composition can be reliably traced to differences in evolution, we are undertaking a transmission spectroscopy survey with JWST to compare the compositions of a sample of hot Jupiters that have different orbital alignments around F stars above the Kraft break. Under the assumption that aligned planets migrate through the inner disc, while misaligned planets migrate after disc dispersal, the act of migrating through the inner disc should cause a measurable difference in the C/O between aligned and misaligned planets. We expect the amplitude and sign of this difference to depend on the amount of planetesimal accretion and whether silicates accreted from the inner disc release their oxygen. Here, we identify all known exoplanets that are suitable for testing this hypothesis, describe our JWST survey, and use noise simulations and atmospheric retrievals to estimate our survey’s sensitivity. With the selected sample of four aligned and four misaligned hot Jupiters, we will be sensitive to the predicted differences in C/O between aligned and misaligned hot Jupiters for a wide range of model scenarios.
Moving the Goalposts? Mutual Fund Benchmark Changes and Relative Performance Manipulation
Authors: Mullally Kevin , Rossi Andrea
Published: October 2024

We analyze changes to mutual funds’ self-declared benchmarks using hand-collected data from funds’ prospectuses. Under existing rules, funds can freely change their benchmark indexes and, implicitly, the historical returns to which they compare their past performance. Funds exploit this loophole by adding (dropping) indexes with lower (higher) past returns, thereby materially improving the appearance of their benchmark-adjusted returns. High-fee funds, broker-sold funds, and funds experiencing poor performance and outflows are more likely to engage in this behavior. These funds subsequently attract additional flows despite continuing to underperform their peers.
Susceptibility of olive cultivars and selections to Colletotrichum species causing anthracnose in Spain
Authors: Exposito-Diaz Anabel , Camiletti Boris X. , Garcia-Lopez M. Teresa , Cabello Diego , Prusky Dov , Diez Concepción M. , Moral Juan
Published: October 2024

Anthracnose, the most critical fruit disease affecting olive crops, necessitates the evaluation of the susceptibility of traditional and new varieties. In Spain and Portugal, Anthracnose is caused by several Colletotrichum species, with C. godetiae and C. nymphaeae being dominant and C. acutatum and C. fioriniae being secondary. This study explores the susceptibility of fruits from an F1 progeny resulting from a cross between 'Picual' (resistant) and 'Arbequina' (moderately susceptible) cultivars to C. godetiae. While most genotypes showed resistance levels comparable to their parents, seven showed a 50% reduction in disease severity compared to ‘Picual.’ The normal distribution of genotypes' response to the pathogen suggests a complex resistance mechanism. Furthermore, we assessed the susceptibility of four traditional cultivars, two new cultivars (‘Sikitita-2’ and ‘Martina’), and five advanced selections (pre-commercial genotypes) to C. godetiae and C. nymphaeae. Despite the significant interaction between the olive genotype and Colletotrichum species in this experiment, the new cultivars and advanced selections were classified as susceptible or moderately susceptible against both species. A subsequent analysis of the interaction between ‘Picual’ (resistant) and ‘Hojiblanca’ (susceptible) fruits with the four mentioned Colletotrichum species revealed significant differences among cultivars but no interaction between genotype and pathogen species. Colletotrichum species were categorized as follows: i) C. godetiae and C. nymphaeae as highly virulent, ii) C. acutatum as moderately virulent, and iii) C. fioriniae as weakly virulent. Finally, C. nymphaeae exhibited an enhanced ability to infect and develop acervuli in olive leaves, potentially serving as an inoculum source for this species. The absence of a correlation between leaf and fruit susceptibilities to the pathogen suggests differences in resistance mechanisms. In conclusion, this study provides valuable insights into the complex interactions between olive genotype and Colletotrichum species, essential for cultivar selection and understanding the disease cycle.
Changes in Diaphragm Intrusion and Thoracic Dimensions After Posterior Spinal Fusion in Patients With Neuromuscular Scoliosis
Authors: Benes Gregory , Gabos Peter G. , Redding Gregory J. , Hunsberger Joann , Cahill Patrick ,   Harms Study Group, Sponseller Paul D.
Published: October 2024

Background:

Cerebral palsy (CP) can cause scoliosis with large thoracolumbar or lumbar curves. Such curves may impair pulmonary function by causing the abdomen and diaphragm to encroach on the thorax. Our purpose was to investigate changes in diaphragm position and other thoracic radiographic measurements at 2 years after posterior spinal fusion (PSF).

Methods:

Retrospective review of data from 56 pediatric patients (Gross Motor Function Classification System >3) who underwent PSF for CP–related (neuromuscular) scoliosis at one US academic hospital from 2010 to 2018. In this study, we used radiographs taken preoperatively and 2 years after PSF to measure lung volume, diaphragm intrusion index (DII), diaphragm vertebral level (DVL), space available for the lung (SAL), and T1-S1 height.

Results:

Lung volume had increased by a mean 902 cm3 (range, –735 to 2697 cm3) at 2-year follow-up. DII improved from a mean (and SD) of 61%±12% to 71%±11% on the left side and 58%±14% to 68%±11% on the right (P<0.001). DVL increased caudally by a mean 1.2 vertebral levels bilaterally, with a mean postoperative position between T8 and T9. Lung space became more symmetrical as the SAL increased from 0.76 to 0.91 (P<0.001). T1-S1 height increased by a mean 7.5±4.3 cm.

Conclusions:

These findings suggest a new way to understand changes in thoracic volume and redistribution of thoracic and lumbar balance when correcting the collapsing spinal deformity in CP. A more caudal postoperative diaphragm position with less diaphragm intrusion into the thorax may reflect an improved length-tension configuration, which could in turn produce greater diaphragmatic strength and endurance.

Level of Evidence:

Level III
Development and Validation of a Machine Learning Model for Early Detection of Untreated Infection
Authors: Buell Kevin G. , Carey Kyle A. , Dussault Nicole , Parker William F. , Dumanian Jay , Bhavani Sivasubramanium V. , Gilbert Emily R. , Winslow Christopher J. , Shah Nirav S. , Afshar Majid , Edelson Dana P. , Churpek Matthew M.
Published: October 2024

BACKGROUND:

Early diagnostic uncertainty for infection causes delays in antibiotic administration in infected patients and unnecessary antibiotic administration in noninfected patients.

OBJECTIVE:

To develop a machine learning model for the early detection of untreated infection (eDENTIFI), with the presence of infection determined by clinician chart review.

DERIVATION COHORT:

Three thousand three hundred fifty-seven adult patients hospitalized between 2006 and 2018 at two health systems in Illinois, United States.

VALIDATION COHORT:

We validated in 1632 patients in a third Illinois health system using area under the receiver operating characteristic curve (AUC).

PREDICTION MODEL:

Using a longitudinal discrete-time format, we trained a gradient boosted machine model to predict untreated infection in the next 6 hours using routinely available patient demographics, vital signs, and laboratory results.

RESULTS:

eDENTIFI had an AUC of 0.80 (95% CI, 0.79–0.81) in the validation cohort and outperformed the systemic inflammatory response syndrome criteria with an AUC of 0.64 (95% CI, 0.64–0.65; p < 0.001). The most important features were body mass index, age, temperature, and heart rate. Using a threshold with a 47.6% sensitivity, eDENTIFI detected infection a median 2.0 hours (interquartile range, 0.9–5.2 hr) before antimicrobial administration, with a negative predictive value of 93.6%. Antibiotic administration guided by eDENTIFI could have decreased unnecessary IV antibiotic administration in noninfected patients by 10.8% absolute or 46.4% relative percentage points compared with clinicians.

CONCLUSION:

eDENTIFI could both decrease the time to antimicrobial administration in infected patients and unnecessary antibiotic administration in noninfected patients. Further prospective validation is needed.
Serum levels of total bile acids are associated with an increased risk of HCC in patients with cirrhosis
Authors: El-Serag Hashem B. , Thrift Aaron P. , Duong Hao , Ning Jing , Khaderi Saira , Singal Amit G. , Asrani Sumeet K. , Marrero Jorge A. , Powell Hannah , Rizwan Kinza , Najjar Omar , Amos Christopher I. , Luster Michelle , Al-Sarraj Abeer , Salem Emad , Scheurer Michael E. , Chhatwal Jagpreet , Kaochar Salma , Kanwal Fasiha
Published: October 2024

Background:

Previous studies have reported higher circulating bile acid levels in patients with HCC compared to healthy controls. However, the association between prediagnostic bile acid levels and HCC risk among patients with cirrhosis is unclear.

Methods:

We measured total BA (TBA) concentration in serum samples collected from a prospective cohort of patients with cirrhosis who were followed until the development of HCC, death, or last study date. Competing risk proportional hazard–adjusted models were used to estimate the association between tertiles of serum TBA levels and the risk of developing HCC. We quantified the incremental predictive value of serum bile acid when added to a previously validated clinical model.

Results:

We analyzed data from 940 patients with cirrhosis, of whom 68 patients progressed to HCC during 3406 person-years of follow-up. Higher baseline serum TBA level was significantly associated with an increased risk of developing HCC with an adjusted HR of 3.69 (95% CI = 1.85–7.37) for the highest versus lowest tertile. TBA levels significantly increased predictive ability for progression to HCC at 2 years of follow-up; the c statistic increased from 0.74 to 0.80 (p < 0.001). There was evidence for a significant interaction between TBA level and hepatitis C (p = 0.04).

Conclusions:

In a large prospective cohort study, the prediagnostic serum level of TBAs was associated with a significant increase in the risk of developing HCC among patients with multi-etiology cirrhosis. The TBA-associated risk was additive to that of established demographic and clinical predictors.
In-vivo tissue healing mechanism at the intestinal anastomosis site following high-frequency electric welding
Authors: Zhu Caihui , Na Yuyan , Yan Zhengqing , Cheng Xiujun , Xie Pengyao , Tao Xiaonan , Chen Lei , Zhao Hui , Qiu Jian , Gu Xiaodong , Xiang Jianbin , Liu Kefu
Published: October 2024

To investigate the effect of high-frequency electric welding (HFEW) on intestinal tissue healing, we performed end-to-end anastomosis experiments in New Zealand rabbits. Within one week post-surgery, animals exhibited normal vital signs, replaced necrotic tissue with healthy collagen, and showed improved tissue strength while inflammation decreased. By day 60, tissue pathology and function fully recovered, resembling normal tissue. Healing at the anastomotic site occurred in three phases: immediate adhesion, inflammation, and remodeling, with macrophages crucial for phagocytosis and regeneration of necrotic tissue. This study enhances understanding of HFEW’s healing mechanisms and supports further preclinical investigations.
Evaluation of balloon sinuplasty for the treatment of pediatric chronic rhinosinusitis
Authors: Fadel Mark A. , Ramaswamy Uma S.
Published: October 2024

Purpose of review

This year marks 10 years from the publication of the clinical consensus statement on pediatric chronic rhinosinusitis (CRS). Balloon sinuplasty did not meet criteria for consensus at that time because there was insufficient evidence on its efficacy and safety. The purpose of this review is to summarize the current evidence on balloon sinuplasty treatment for pediatric CRS.

Recent findings

Balloon sinuplasty is not a cost-effective measure compared to adenoidectomy and endoscopic sinus surgery (ESS). In the pediatric population, benefits include short operative time, reduced tissue manipulation, and potential for decreased antibiotic courses. Alternatively, balloon dilation has increased equipment costs and there is a lack of robust prospective data that fully elucidates balloon sinuplasty's role in the management of pediatric CRS.

Pediatric otolaryngologists should continue to perform first-line adenoidectomy and consider ESS based on imaging and other validated clinical scoring systems. Balloon sinuplasty has not yet been proven as an effective treatment for pediatric CRS and further large-scale investigations are required to overcome its lack of cost-effectiveness.
Exploring Reasons for Satisfaction with Job Assignments Among Travel Nurses
Authors: Owens Sharon , West Barbara , Watson Heather
Published: October 2024

OBJECTIVE

The aim of this study was to explore factors related to a travel nurse completing or extending an assignment or leaving before the end of an assignment.

BACKGROUND

Hospitals use various options for staffing shortages. One option is to contract with travel nurses. The recent increase in travel nurse utilization, coupled with the need to retain permanent staff and see a return on investment, requires an understanding of factors driving travel nurse decision-making.

METHODS

This qualitative research used semistructured interviews and a survey with prepandemic-postpandemic participants that comprised travel nurses from 2 urban academic centers.

RESULTS

Three themes emerged from the interview data: flexibility, support, and conditions.

CONCLUSIONS

Travel nurses report they will stay in an assignment if they feel supported and have flexibility and if the location is desirable. Matching institutional needs with travel nurse experience and assignment expectations can create a mutually beneficial experience for the institution, agency, and the travel nurse.
Improving Access to Hygiene, Sanitation, and Drinking Water in King County and Beyond: Success Factors and Costs
Authors: Holme Francesca , Kellogg Ryan , Andu Semone , Wasse Jessica Knaster , Seinfeld Keith , Gelb Richard
Published: October 2024

Context

Most major urban areas in the US, including Seattle and King County, have a long-standing lack of public restrooms, handwashing stations, and drinking water, presenting public health risks.

Objective

To aid decision-makers in expanding access, we review available information regarding successful hygiene programs in urban settings to identify shared characteristics and costs.

Design

We reviewed 10 journal articles, 49 news articles, and 54 pieces of gray literature including reports, white papers, and online resources describing real-world hygiene, sanitation, and drinking water programs in US and global urban settings. We selected programs in 8 cities and applied a thematic analysis to identify shared success factors. We also summarized costs where available.

Settings

Calgary (Canada), Denver (Colorado), London (United Kingdom), Los Angeles (California), Portland (Oregon), San Francisco (California), Seattle (Washington), and Vancouver (Canada).

Results

Successful programs usually provide frequent cleaning and maintenance, are designed and operated to discourage crime and misuse, leverage existing infrastructure, and include mobile solutions. Cities can expect an initial cost of at least $133 000 per toilet and annual operating costs of at least $100 000 per toilet.

Conclusions

By employing proven solutions and bringing them to scale over time, cities can promote health while improving quality of life and facilitating movement through public spaces for all. Costs should be understood in the context of expenses such as sidewalk cleaning and human waste removal that are necessitated by a lack of restrooms.
Vesicle-based formulations for pain treatment: a narrative review
Authors: Martinez Juan , Ingram Nicola , Kapur Nikil , Jayne David G. , Beales Paul A.
Published: October 2024

Pain, a complex and debilitating condition, necessitates innovative therapeutic strategies to alleviate suffering and enhance patients' quality of life. Vesicular systems hold the potential to enhance precision of drug localisation and release, prolong the duration of therapeutic action and mitigate adverse events associated with long-term pharmacotherapy. This review critically assesses the current state-of-the-art in vesicle-based formulations (liposomes, polymersomes, ethosomes, and niosomes) for pain management applications. We highlight formulation engineering strategies used to optimise drug pharmacokinetics, present preclinical findings of experimental delivery systems, and discuss the clinical evidence for the benefits of clinically approved formulations. We present the challenges and outlook for future improvements in long-acting anaesthetic and analgesic formulation development.
Design of novel test rig for prosthetic finger distal interphalangeal and phalanx strengths
Authors: R Madhu Mohan , Kattimani Subhaschandra , Koorata Poornesh Kumar , C Girisha
Published: October 2024

Testing is one of the most significant phases of any engineering process, the last process followed by conceptualization, designing, and fabricating. If the testing outcomes are not genealogy sensible measurables, then eventually it calls for a redesign overhaul. Existing testing equipment to analyze the load and failures are conventional digital universal testing machines with minimum jigs and fixtures. In addition, the existing fixtures cannot be adapted to the anatomy of a human finger. Consequently, the present work explores the best possible design of a jig for testing the naturally articulated movement of a human finger (prosthetic wear-on). Furthermore, the present jig design checks a wide range of parameters such as freedom of motion, a path along with curvature, load, failures, and intermittent positions of applied load, which is adaptable to existing universal testing machines available for broader applications.
Distribution of Specialties Providing Surgical Management of Cleft-Related Speech Disorders in Children 3 years of Age and Older: 2004 to 2021
Authors: Garg Stuti P. , Chwa Emily S. , Reddy Narainsai K. , Shah Krish V. , Weissman Joshua P. , Gosain Arun K.
Published: October 2024

Given the overlap in specialties performing secondary correction of velopharyngeal incompetence (VPI), the present study investigated the specialty distribution for surgical providers of cleft care from 2004 to 2021. Data were obtained from 45 hospitals from 2004 to 2021 through the Pediatric Health Information System database. Cases of secondary surgical management of VPI were retrieved, identifying the year of surgery and specialty of the providing surgeon. A total of 7090 procedures were included in this study, of which 36.0% were secondary palatoplasty/lengthening, 34.1% were sphincter pharyngoplasty, and 29.8% were pharyngeal flap. Secondary management of VPI was performed by plastic surgeons (67%), otolaryngologists (31%), and oral and maxillofacial surgeons (OMFS, 12%). Palatal revision and/or lengthening procedures were the most common secondary procedure performed by plastic surgeons (42%) and OMFS (64%), whereas sphincter pharyngoplasty was the most common procedure performed by otolaryngologists (55%; P<0.001). The proportion of sphincter pharyngoplasty performed by plastic surgeons significantly decreased from 2017-2021 (P<0.05). Plastic surgeons performed most procedures for secondary management of VPI from 2004 to 2021, followed by otolaryngologists and OMFS. The type of procedure selected for secondary management of VPI differed significantly between the provider’s specialty, with otolaryngologists more likely to perform sphincter pharyngoplasty.
Failure Mode Effects Analysis of Re-triage of Injured Patients to Receiving High-level Illinois Trauma Centers
Authors: Slocum John D. , Holl Jane L. , Brigode William M. , Voights Mary Beth , Anstadt Michael J. , Henry Marion C. , Mis Justin , Fantus Richard J. , Plackett Timothy P. , Markul Eddie J. , Chang Grace H. , Shapiro Michael B. , Siparsky Nicole , Stey Anne M.
Published: October 2024

Objective:

This study identified failures in emergency inter-hospital transfer, or re-triage, at high-level trauma centers receiving severely injured patients.

Background:

The re-triage process averages 4 hours despite the fact timely re-triage within 2 hours mitigates injury-associated mortality. Non-trauma and low-level trauma centers reported that the most critical failures were in finding an accepting high-level trauma center. Critical failures at high-level trauma centers have not been assessed.

Methods:

This was an observational cross-sectional study at 9 high-level adult trauma centers and 3 high-level pediatric trauma centers. Failure modes effects analysis of the re-triage process was conducted in 4 phases. Phase 1 purposively sampled trauma coordinators, followed by snowball sampling of clinicians, operations, and leadership to ensure representative participation. Phase 2 mapped each re-triage step. Phase 3 identified failures at each step. Phase 4 scored each failure on impact, frequency, and safeguards for detection. Standardized rubrics were used in phase 4 to rate each failure’s impact (I), frequency (F), and safeguard for detection (S) to calculate their risk priority number (RPN; IxFxS). Failures were rank-ordered for criticality based on their RPN.

Results:

A total of 64 trauma coordinators, surgeons, emergency medicine physicians, nurses, operations, and quality managers across 12 high-level trauma centers participated. There were 178 failures identified at adult and pediatric high-level trauma centers. The most critical failures were: (1) insufficiently trained transport staff (RPN = 648), (2) issues transmitting imaging from sending to receiving centers (RPN = 400), and (3) incomplete exchange of clinical information (RPN = 384).

Conclusions:

The most critical failures were limited transportation and incomplete exchange of clinical, radiologic, and arrival timing information. Further investigation of these failures includes several regions is needed to determine the reproducibility of these findings.
Symptom management for people with advanced dementia who are receiving end of life care
Authors: Drummond Maria , Johnston Bridget
Published: October 2024

Purpose of review

This review aims to synthesise contemporary research on symptom management for people with advanced dementia who are thought to be in the final year of life. It highlights the unique challenges faced by palliative care and dementia care specialists, offering insights into the clinical decision-making required to support those with advanced dementia in various care settings.

Recent findings

Recent studies indicate that people with advanced dementia often experience significant unmet palliative care needs, particularly regarding symptom management. Pain, breathlessness, and psychological distress are frequently mismanaged, which contributes to suboptimal care. Moreover, the unpredictable trajectory of dementia complicates the identification of end-of-life needs, which can result in fragmented care. Caregivers, both professional and family, struggle with managing complex symptoms, while family caregivers in home settings face added burdens in providing care without sufficient support.

Palliative care for people with advanced dementia is currently inadequate due to a lack of tailored interventions, poor symptom management, and disjointed care systems. Enhancing training for caregivers, fostering interdisciplinary collaboration, and focusing on integrated care approaches across home and institutional settings are crucial to improving quality of life and symptom control for people with advanced dementia.
Early Complications in Kidney Donors and Course of Health-related Quality of Life 12 mo After Donation: An Analysis of the Swiss Organ Living-Donor Health Registry
Authors: Brügger Charlotte , Hunkeler Zoé , Diebold Matthias , Krättli Joana , Geiger Irene , Wehmeier Caroline , Wolff Thomas , Vogt Bruno , Storni Federico , Golshayan Dela , Zingg Tobias , de Seigneux Sophie , Haidar Fadi , Binet Isabelle , Schnyder Aurelia , Hübel Kerstin , Müller Thomas , Rössler Fabian , Steiger Jürg , Hirt-Minkowski Patricia
Published: October 2024

Background.

Since 1998, the Swiss Organ Living-Donor Health Registry (SOL-DHR) has recorded peri- and postoperative complications of living kidney (LK) donors, as reported by all Swiss transplant centers and has collected follow-up data prospectively.

Methods.

We analyzed the early complications of 2379 consecutive individuals who donated a kidney between January 1998 and June 2022 and assessed their health-related quality of life (HRQoL) 1 y after donation.

Results.

In total, 447 early complications in 404/2379 LK donors (17.0%) were reported to the SOL-DHR. The frequency of donors with major complications (ie, Dindo-Clavien classification 3/4) was 2.4%. In total, 31 donors needed reoperation, and in 13/31 (42%), donors reoperation was necessary because of bleeding complications. Independent risk factors for major early complications were older donor age (P = 0.005) and type of surgical approach (ie, the laparoscopic retroperitoneal compared with laparoscopic transabdominal surgery; P = 0.01), but not sex. We observed a U-shaped association of body mass index, where very low/high body mass indexes had higher odds of major early complications, without reaching statistical significance. Although HRQoL was affected by kidney donation, 96.5% of donors indicated that they would donate their kidney again. The only independent risk factor for low HRQoL based on mental health scores was worsening EB after living kidney donation (P < 0.0001).

Conclusions.

Overall, living kidney donation is a safe procedure, however, donor age and type of surgical approach affect the risk of complications. A decline in emotional bonding with the recipient after donation may worsen the quality of life of the donor.
Simultaneous Pancreas-Kidney Transplant Outcomes Stratified by Autoantibodies Status and Pretransplant Fasting C-peptide
Authors: Parajuli Sandesh , Tamburrini Riccardo , Aziz Fahad , Dodin Ban , Astor Brad C. , Mandelbrot Didier , Kaufman Dixon , Odorico Jon
Published: October 2024

Backgrounds.

Pancreatic beta cell function and islet autoantibodies classically distinguish types of diabetes (type 1 diabetes mellitus [DM] or type 2 DM). Here, we sought to evaluate simultaneous pancreas-kidney (SPK) transplant outcomes stratified by the presence or absence of beta cell function and autoantibodies.

Methods.

SPK recipients were eligible if pretransplant autoantibodies were measured against insulin, islet cell, or glutamic acid decarboxylase 65-kD isoform. Recipients were categorized as A+ or A– based on the detection of ≥1 autoantibodies. Recipients were similarly categorized on the basis of detectable pretransplant fasting C-peptide of ≥2 ng/mL (β+) or <2 ng/mL (β–). Thus, recipients were categorized into 4 groups: A+β–, A–β–, A–β+, and A+β+. Outcomes of interest were overall pancreas graft failure (non–death-censored), death-censored pancreas, or kidney graft failure (death-censored pancreas graft failure [DCGF]; kidney DCGF), composite outcomes with any of the 3 outcomes as pancreas DCGF, use of an antidiabetic agent, or hemoglobin A1c >6.5.

Results.

One hundred eighty-three SPK recipients were included: A+β– (n = 72), A–β– (n = 42), A–β+ (n = 49), and A+β+ (n = 20). We did not detect a statistical difference in non–death-censored pancreas graft failure for A+β– recipients compared with other groups: A–β– (adjusted hazard ratio [aHR]: 0.44; 95% confidence interval [CI], 0.14-1.42), A–β+ (aHR: 1.02; 95% CI, 0.37-2.85), and A+β+ (aHR: 0.67; 95% CI, 0.13-3.33) in adjusted analyses. Similar outcomes were observed for other outcomes.

Conclusions.

In SPK recipients, outcomes were similar among recipients with classic features of type 1 DM and various other types of DM.
Spectrum of respiratory viruses identified from SARS-CoV-2-negative human respiratory tract specimens in Watansoppeng, Indonesia
Authors: Idris Irfan , Wahid Isra , Antonjaya Ungke , Johar Edison , Kleib Fiqry Hasan , Sriyani Ida Yus , Dewantari Aghnianditya Kresno , Daming Oderna , Duharing Mustakim , Sappe Fatmawati , Hasan Hajar , Yudhaputri Frilasita Aisyah , Syafruddin Din , Myint Khin Saw Aye
Published: October 2024

Respiratory infections account for millions of hospital admissions worldwide. The aetiology of respiratory infections can be attributed to a diverse range of pathogens including viruses, bacteria and fungi. SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)-negative specimens from Wattansoppeng city, South Sulawesi, were analysed to study the spectrum of respiratory viruses. Samples were screened for influenza virus, enterovirus, Paramyxoviridae, Nipah virus, Coronaviridae and Pneumoviridae. Of 210 specimens, 19 were positive for respiratory syncytial virus (RSV)-A, RSV-B, human parainfluenza virus type 1 (HPIV-1), HPIV-2, human rhinovirus (HRV)-A, HRV-B, HRV-C, human metapneumovirus (HMPV), influenza A virus (IAV) and coxsackievirus A6 (CV-A6). Influenza virus was of seasonal H3N2 subtype. The HMPVs were of genotypes B1 and A2a, while one RSV-A was of the ON-1 genotype. The viruses mostly affected children with unknown severity.
Molecular characteristics of CTX-M β-lactamase-producing and quinolone-resistant Escherichia coli among deer in a popular tourist spot in Japan
Authors: Ikushima Shiori , Sugiyama Michiyo , Asai Tetsuo
Published: October 2024

Introduction: Antimicrobial resistance (AMR) is a growing global concern. Clonal lineages of CTX-M β-lactamase-producing Escherichia coli (CTXE) and quinolone-resistant E. coli (QREC) were disseminated among deer population in a famous tourist destination (Nara Park; NP) in Japan.
Hypothesis or gap statement: The molecular characteristics of CTXE or QREC isolates which could pose a threat to public health has not been elucidated.
Aim: This study aimed to characterize the genetic traits of CTXE and QREC isolates derived from NP deer and compare them with lineages prevalent worldwide.
Methodology: Sixteen CTXE and three QREC isolates recovered from NP deer feces between 2018 and 2020 were analyzed using whole-genome sequencing. For endemic lineages, phylogenetic trees were constructed against the isolates registered in EnteroBase database using the core genome single nucleotide polymorphism scheme.
Results: The most prevalent lineage in NP deer was ST3580. Several pandemic lineages, such as sequence type (ST) 38, ST58, and ST117, were included. The QREC lineages prevalent among deer were designated as extra-intestinal pathogenic E. coli or uropathogenic E. coli. Thirteen of the 24 antimicrobial resistance genes (ARGs) were considered high-risk ARG families. Chromosomal integration of blaCTX-M-15 was observed in all plasmid-negative isolates. Phylogenetic analysis suggested relationships between NP isolates and isolates sourced from environment or poultry.
Conclusion: ST3580 has high potential to disseminate clonally. Furthermore, multiple clinically relevant lineages of CTXE and QREC are endemic in NP deer; however, they could be less virulent than isolates belonging to the same lineages which could cause severe infectious diseases. Further studies are required to investigate the relationship between chromosomal integration of plasmid-encoded genes and the stable propagation of AMR bacteria in wildlife and the environment.
Singapore grouper iridovirus VP12 evades the host antiviral immune response by targeting the cGAS-STING signalling pathway
Authors: Zhang Luhao , Xu Linting , Zhang Xin , Liao Jiaming , Kang Shaozhu , Wu Siting , Qin Qiwei , Wei Jingguang
Published: October 2024

The emergence of Singapore grouper iridovirus (SGIV) has caused huge losses to grouper farming. SGIV is a DNA virus and belongs to the genus Ranavirus. Groupers infected with SGIV showed haemorrhaging and swelling of the spleen, with a mortality rate of more than 90% within a week. Therefore, it is of great significance to study the escape mechanism of SGIV from host innate immunity for the prevention and treatment of viral diseases in grouper. In this study, the viral proteins that interact with EccGAS were identified by mass spectrometry, and the SGIV VP12 protein that inhibits cyclic GMP–AMP synthase (cGAS)-stimulator of interferon genes (STING)-mediated antiviral innate immunity was screened by the dual-luciferase reporter gene assay. VP12 belongs to the late gene of the virus. The immunofluorescence analysis demonstrated that VP12 was aggregated and distributed in the cytoplasm during the early stage of virus infection and translocated into the nucleus at the late stage of virus infection. VP12 inhibited the activation of IFN3, ISRE and NF-κB promoter activities mediated by cGAS-STING, EcTBK1 and EcIRF3. Quantitative real-time PCR analysis showed that VP12 inhibited the expression of interferon-related genes, including those mediated by cGAS-STING. VP12 enhanced the inhibition of IFN3, ISRE and NF-κB promoter activity by EccGAS, EccGAS-mab-21 and EccGAS-delete-mab21. The interaction between VP12 and EccGAS was found to be domain independent. The immunoprecipitation results demonstrated that VP12 interacted and co-localized with EccGAS, EcTBK1 and EcIRF3. VP12 degraded the protein levels of EcTBK1 and EcIRF3 and degraded EcIRF3 through the protease pathway. These results suggest that SGIV VP12 protein escapes the cGAS-STING signalling pathway and degrades EcIRF3 protein expression through the protease pathway.
Tissue response in a rat model of denture stomatitis treated with tissue conditioner containing antifungal complexed with β-cyclodextrin
Authors: Sugio Carolina Yoshi Campos , Cestari Tânia Mary , Garcia Amanda Aparecida Maia Neves , Moraes Gustavo Simão , Albach Thaís , de Oliveira Thais Marchini , Garlet Gustavo Pompermaier , Urban Vanessa Migliorini , Neppelenbroek Karin Hermana
Published: October 2024

Introduction. Tissue conditioners modified with antifungals are a potential alternative to denture stomatitis (DS) treatment.

Gap Statement. Information on tissue response to this treatment before its clinical application is lacking.

Aim. This study aimed to evaluate the tissue response of a tissue conditioner modified with antifungals in a rat model of DS.

Methodology. After DS induction for 4 days under antibiotic therapy, Wistar rats had their intraoral devices (IODs) relined with the tissue conditioner Softone without (Soft) or with the MICs against Candida albicans of nystatin (Nys) or chlorhexidine (Chx) complexed or not with β-cyclodextrin (Nys:βCD and Chx:βCD). Three controls were included: healthy rats [negative control (Nc)], rats using a sterile IOD [sterile device (Sd)] and rats with DS that did not receive treatment (DS). After 4 days of treatment, the palatal mucosa under the IODs underwent histological processing for morphohistopathological and histometric analyses, morphology of collagen fibres (birefringence), immunohistochemistry for the expression of cell proliferation (proliferating cell nuclear antigen) and cytokine (IL-1β).

Results. The Nc and Sd groups were similar (P>0.05), displaying epithelial and connective tissues without any discernible changes in the parameters assessed. The DS and Soft groups exhibited pronounced epithelial alterations, cell proliferation and expression of the cytokine IL-1β. In groups treated with drug incorporation (Nys, Chx, Nys:βCD and Chx:βCD), all samples demonstrated a reduction in tissue inflammation or complete tissue recovery, with an epithelium compatible with health. For the immunohistochemical parameters, the Chx, Nys:βCD and Chx:βCD groups were comparable with Nc (P>0.05).

Conclusion. The proposed treatment could be promising for DS, as it led to the tissue recovery of the palatal mucosa. Nevertheless, much lower concentrations of complexed antifungals were required to achieve a similar or higher degree of tissue response compared with uncomplexed drugs in a modified tissue conditioner formulation.
The mineralization of osteonal cement line depends on where the osteon is formed
Authors: Cantamessa A. , Blouin S. , Rummler M. , Berzlanovich A. , Weinkamer R. , Hartmann M.A. , Ruffoni D.
Published: October 2024

The cement line (CL) is a thin layer separating secondary osteons from interstitial bone and other osteons. It is assumed to play a significant role in bone fracture resistance, owing to its ability to deflect or arrest microcracks. Despite the possible role for bone quality, the CL is still one of the least understood microstructural features of bones, with unknowns on CL composition, mineralization, and mechanical properties. This study, focusing on CL mineralization, aims to elucidate the interplay between the mineral content of the CL and of adjacent bone tissue. Using quantitative backscattered electron imaging, osteons with different degrees of mineralization coming from human femoral samples were analyzed. We implemented a spatially resolved analysis of the mineral content in layers along the CL, considering both regions inside the osteon (i.e., formed soon after CL deposition) and outside (i.e., already present at the time of CL deposition). We found that the mineral content of the CL correlates strongly with the mineral content outside of the osteon, but not inside. Assuming the mineral content of the osteon as a proxy of its age, we demonstrate that not only the osteon, but also the CL increases its mineral content with time. However, the rate of increase is lower in the CL. Importantly, the specific value of the high initial mineral content of the CL depends on the mineral content of the local surrounding, in which the osteon was formed. Our findings highlight the central role of the local degree of mineralization of the bone around the osteon for building the CL.
A novel approach to digital characterisation of Tertiary Lymphoid Structures in colorectal cancer
Authors: Munoz-Erazo Luis , Park Saem Mul , Lin Shelly , Chen Chun-Jen J. , Zhou Lisa Y.Y. , Rhodes Janet L , Jeon Taesung , Fenton Sonya , McCall John L. , Kemp Roslyn A. , Dunbar P. Rod
Published: October 2024

Tertiary Lymphoid Structures (TLS) in cancer tissue are potential sites for the organisation of immune responses to cancer, and correlate positively with improved clinical outcomes for patients including in colorectal cancer (CRC). However it has proven challenging to standardise assessment of TLS due to the highly variable appearances of circumscribed domains of TLS within tissue sections. A recent three-dimensional reconstruction of TLS in CRC tissue showed that TLS are often large, multi-lobular structures, suggesting that assessing TLS across whole sections may be necessary to provide an accurate view of TLS activity in a patient’s tumour. In a pilot study we therefore used whole slide scans of multiplexed immunofluorescence images to characterise TLS from 22 subjects with CRC. Multiplexed staining for CD20, CD3, CD8, FoxP3 and Ki-67 enabled us to identify B-cells, CD8+ T cells, FoxP3– CD4 T-cells, and Foxp3+ CD4 T cells in all sections, and quantify both the presence of these cell subsets in lymphocytic clusters and their degree of proliferation within those clusters. In total we identified 524 lymphocytic clusters with morphology consistent with TLS. The count of TLS domains varied substantially between samples (from 4 to 100, mean 24) as did the proportion of total section area occupied by TLS (0.2%-7.8%) as well as size, morphology and cellular constituents; reflecting the intersection of the section plane with complex 3-dimensional structures. We quantified proliferation of B-cells and T-cell subsets within TLS domains across entire sections and compared to the canonical approach of counting and phenotyping individual TLS domains. The whole-slide approach proved far simpler than the canonical approach, generating digital summaries across our sample set clearly identifying patients with strikingly different levels of immune activity within their TLS. It also allowed us to demonstrate strong correlations between the proliferation of B-cells within CRC TLS and that of T-cell subsets. In summary we find that whole-section digital quantification of immune cell activity within TLS has major advantages over canonical approaches. Such whole-section approaches should accelerate research into correlations between TLS status and clinical outcomes, and ultimately enable standardised clinical tests based on automated analysis of multiplexed images.