bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of peri- and intraoperative outcomes of open vs robotic-assisted partial nephrectomy for renal cell carcinoma: a propensity-matched analysis
Authors: Hoeh Benedikt , Wenzel Mike , Eckart Olivia , Fleisgarten Felicia , Garcia Cristina Cano , Köllermann Jens , Würnschimmel Christoph , Larcher Alessandro , Karakiewicz Pierre , Kluth Luis A. , Chun Felix K. H. , Mandel Philipp , Becker Andreas
Published: June 2023

Background

Partial nephrectomy (PN) is the gold standard surgical treatment for resectable renal cell carcinoma (RCC) tumors. However, the decision whether a robotic (RAPN) or open PN (OPN) approach is chosen is often based on the surgeon’s individual experience and preference. To overcome the inherent selection bias when comparing peri- and postoperative outcomes of RAPN vs. OPN, a strict statistical methodology is needed.

Materials and methods

We relied on an institutional tertiary-care database to identify RCC patients treated with RAPN and OPN between January 2003 and January 2021. Study endpoints were estimated blood loss (EBL), length of stay (LOS), rate of intraoperative and postoperative complications, and trifecta. In the first step of analyses, descriptive statistics and multivariable regression models (MVA) were applied. In the second step of analyses, to validate initial findings, MVA were applied after 2:1 propensity-score matching (PSM).

Results

Of 615 RCC patients, 481 (78%) underwent OPN vs 134 (22%) RAPN. RAPN patients were younger and presented with a smaller tumor diameter and lower RENAL-Score sum, respectively. Median EBL was comparable, whereas LOS was shorter in RAPN vs. OPN. Both intraoperative (27 vs 6%) and Clavien-Dindo > 2 complications (11 vs 3%) were higher in OPN (both < 0.05), whereas achievement of trifecta was higher in RAPN (65 vs 54%; p = 0.028). In MVA, RAPN was a significant predictor for shorter LOS, lower rates of intraoperative and postoperative complications as well as higher trifecta rates. After 2:1 PSM with subsequent MVA, RAPN remained a statistical and clinical predictor for lower rates of intraoperative and postoperative complications and higher rates of trifecta achievement but not LOS.

Conclusions

Differences in baseline and outcome characteristics exist between RAPN vs. OPN, probably due to selection bias. However, after applying two sets of statistical analyses, RAPN seems to be associated with more favorable outcomes regarding complications and trifecta rates.
Factors predicting recurrence after left‑sided pancreatectomy for pancreatic ductal adenocarcinoma
Authors: Xia Tao , Xu Peng , Mou Yiping , Zhang Xizhou , Song Shihao , Zhou Yucheng , Lu Chao , Zhu Qicong , Xu Yunyun , Jin Weiwei , Wang Yuanyu
Published: June 2023

Background

Recurrence after resection is the main factor for poor survival. The relationship between clinicopathological factors and recurrence after curative distal pancreatectomy for PDAC has rarely been reported separately.

Methods

Patients with PDAC after left‑sided pancreatectomy between May 2015 and August 2021 were retrospectively identified.

Results

One hundred forty-one patients were included. Recurrence was observed in 97 patients (68.8%), while 44 (31.2%) patients had no recurrence. The median RFS was 8.8 months. The median OS was 24.9 months. Local recurrence was the predominant first detected recurrence site (n = 36, 37.1%), closely followed by liver recurrence (n = 35, 36.1%). Multiple recurrences occurred in 16 (16.5%) patients, peritoneal recurrence in 6 (6.2%) patients, and lung recurrence in 4 (4.1%) patients. High CA19-9 value after surgery, poor differentiation grade, and positive lymph nodes were found to be independently associated with recurrence. The patients receiving adjuvant chemotherapy had a decreased likelihood of recurrence. In the high CA19-9 value cohort, the median PFS and OS of the patients with or without chemotherapy were 8.0 VS. 5.7 months and 15.6 VS. 13.8 months, respectively. In the normal CA19-9 value cohort, there was no significant difference in PFS with or without chemotherapy (11.7 VS. 10.0 months, P = 0.147). However, OS was significantly longer in the patients with chemotherapy (26.4 VS. 13.8 months, P = 0.019).

Conclusions

Tumor biologic characteristics, such as T stage, tumor differentiation and positive lymph nodes, affecting CA19-9 value after surgery are associated with patterns and timing of recurrence. Adjuvant chemotherapy significantly reduced recurrence and improved survival. Chemotherapy is strongly recommended in patients with high CA199 after surgery.
Prognostic value of consolidation-to-tumor ratio on computed tomography in NSCLC: a meta-analysis
Authors: Wu Yongming , Song Wenpeng , Wang Denian , Chang Junke , Wang Yan , Tian Jie , Zhou Sicheng , Dong Yingxian , Zhou Jing , Li Jue , Zhao Ziyi , Che Guowei
Published: June 2023

Background

Although several studies have confirmed the prognostic value of the consolidation to tumor ratio (CTR) in non-small cell lung cancer (NSCLC), there still remains controversial about it.

Methods

We systematically searched the PubMed, Embase, and Web of Science databases from inception to April, 2022 for eligible studies that reported the correlation between CTR and prognosis in NSCLC. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were extracted and pooled to assess the overall effects. Heterogeneity was estimated by I2 statistics. Subgroup analysis based on the cut-off value of CTR, country, source of HR and histology type was conducted to detect the sources of heterogeneity. Statistical analyses were performed using STATA version 12.0.

Results

A total of 29 studies published between 2001 and 2022 with 10,347 patients were enrolled. The pooled results demonstrated that elevated CTR was associated with poorer overall survival (HR = 1.88, 95% CI 1.42–2.50, P < 0.01) and disease-free survival (DFS)/recurrence-free survival (RFS)/progression-free survival (PFS) (HR = 1.42, 95% CI 1.27–1.59, P < 0.01) in NSCLC. According to subgroup analysis by the cut-off value of CTR and histology type, both lung adenocarcinoma and NSCLC patients who had a higher CTR showed worse survival. Subgroup analysis stratified by country revealed that CTR was a prognostic factor for OS and DFS/RFS/PFS in Chinese, Japanese, and Turkish patients.

Conclusions

In NSCLC patients with high CTR, the prognosis was worse than that with low CTR, indicating that CTR may be a prognostic factor.
Downregulated DUXAP8 lncRNA impedes trophoblast cell proliferation and migration by epigenetically upregulating TFPI2 expression
Authors: Tang Xiaotong , Cao Yueying , Wu Dan , Sun Lizhou , Xu Yetao
Published: June 2023

Background

Preeclampsia (PE), a pregnancy complication characterized by new-onset hypertension and proteinuria during the second trimester, is the leading cause of neonatal and maternal morbidity and mortality. In the etiology of PE, failure of uterine spiral artery remodeling may be related to functioning abnormally of trophoblast cells, leading to the occurrence and progression of PE. Recently, long noncoding RNAs (lncRNAs) have been reported to play critical roles in PE nowadays. This study aimed to investigate the expression and functions of the TFPI2 pathway-related lncRNA DUXAP8.

Methods

DUXAP8 expression in the placenta from pregnancies was examined using qPCR. Then, the in vitro functions of DUXAP8 were investigated through MTT, EdU, colony, transwell, and flow cytometry experiments. The downstream gene expression profiles were assessed using RNA transcriptome sequencing analysis and verified using qPCR and western blot. Furthermore, Immunoprecipitation (RIP), chromatin immunoprecipitation (CHIP) and fluorescence in situ hybridization (FISH) were used to detect the interaction between lncDUXAP8/EZH2/TFPI2.

Results

The expression of lncRNA DUXAP8 in placenta of patients with eclampsia was significantly decreased. After knockout of DUXAP8, the proliferation and migration of trophoblasts were significantly decreased, and the percentage of apoptosis was increased. Flow cytometry showed that low expression of DUXAP8 increased the accumulation of cells in G2/M phase, while overexpression of DUXAP8 had the opposite effect. We also proved that DUXAP8 epigenetically inhibited TFPI2 expression by recruiting EZH2 and mediating H3K27me3 modification.

Conclusion

Together, these resulting data clarify that aberrant expression of DUXAP8 is involved in the potential PE development and progress. Unraveling the role of DUXAP8 will provide novel insights into the pathogenesis of PE.
ATXN3 promotes prostate cancer progression by stabilizing YAP
Authors: Wu Longxiang , Ou Zhenyu , Liu Peihua , Zhao Cheng , Tong Shiyu , Wang Ruizhe , Li Yangle , Yuan Junbin , Chen Minfeng , Fan Benyi , Zu Xiongbing , Wang Yongjie , Tang Jianing
Published: June 2023

Background

Prostate cancer (PC) is the most common neoplasm and is the second leading cause of cancer-related deaths in men worldwide. The Hippo tumor suppressor pathway is highly conserved in mammals and plays an important role in carcinogenesis. YAP is one of major key effectors of the Hippo pathway. However, the mechanism supporting abnormal YAP expression in PC remains to be characterized.

Methods

Western blot was used to measure the protein expression of ATXN3 and YAP, while the YAP target genes were measured by real-time PCR. CCK8 assay was used to detect cell viability; transwell invasion assay was used to measure the invasion ability of PC. The xeno-graft tumor model was used for in vivo study. Protein stability assay was used to detect YAP protein degradation. Immuno-precipitation assay was used to detect the interaction domain between YAP and ATXN3. The ubiquitin-based Immuno-precipitation assays were used to detect the specific ubiquitination manner happened on YAP.

Results

In the present study, we identified ATXN3, a DUB enzyme in the ubiquitin-specific proteases family, as a bona fide deubiquitylase of YAP in PC. ATXN3 was shown to interact with, deubiquitylate, and stabilize YAP in a deubiquitylation activity-dependent manner. Depletion of ATXN3 decreased the YAP protein level and the expression of YAP/TEAD target genes in PC, including CTGF, ANKRD1 and CYR61. Further mechanistic study revealed that the Josephin domain of ATXN3 interacted with the WW domain of YAP. ATXN3 stabilized YAP protein via inhibiting K48-specific poly-ubiquitination process on YAP protein. In addition, ATXN3 depletion significantly decreased PC cell proliferation, invasion and stem-like properties. The effects induced by ATXN3 depletion could be rescued by further YAP overexpression.

Conclusions

In general, our findings establish a previously undocumented catalytic role for ATXN3 as a deubiquitinating enzyme of YAP and provides a possible target for the therapy of PC.
Pharmacologic inhibition of NLRP3 reduces the levels of α-synuclein and protects dopaminergic neurons in a model of Parkinson’s disease
Authors: Amo-Aparicio Jesus , Daly Jonathan , Højen Jesper Falkesgaard , Dinarello Charles A.
Published: June 2023

Background

Parkinson’s disease (PD) is characterized by a progressive degeneration of dopaminergic neurons, which leads to irreversible loss of peripheral motor functions. Death of dopaminergic neurons induces an inflammatory response in microglial cells, which further exacerbates neuronal loss. Reducing inflammation is expected to ameliorate neuronal loss and arrest motor dysfunctions. Because of the contribution of the NLRP3 inflammasome to the inflammatory response in PD, we targeted NLRP3 using the specific inhibitor OLT1177®.

Methods

We evaluated the effectiveness of OLT1177® in reducing the inflammatory response in an MPTP neurotoxic model of PD. Using a combination of in vitro and in vivo studies, we analyzed the effects of NLRP3 inhibition on pro-inflammatory markers in the brain, α-synuclein aggregation, and dopaminergic neuron survival. We also determined the effects of OLT1177® on locomotor deficits associated with MPTP and brain penetrance.

Results

Treatment with OLT1177® prevented the loss of motor function, reduced the levels of α-synuclein, modulated pro-inflammatory markers in the nigrostriatal areas of the brain, and protected dopaminergic neurons from degeneration in the MPTP model of PD. We also demonstrated that OLT1177® crosses the blood–brain barrier and reaches therapeutic concentrations in the brain.

Conclusions

These data suggest that targeting the NLRP3 inflammasome by OLT1177® may be a safe and novel therapeutic approach to arrest neuroinflammation and protect against neurological deficits of Parkinson’s disease in humans.
The role of implementation organizations in scaling evidence-based psychosocial interventions
Authors: Crane Margaret E. , Kendall Philip C. , Chorpita Bruce F. , Sanders Matthew R. , Miller Allen R. , Webster-Stratton Carolyn , McWilliam Jenna , Beck Judith S. , Ashen Ceth , Embry Dennis D. , Pickering John A. , Daleiden Eric L.
Published: June 2023

Background

To bring evidence-based interventions (EBIs) to individuals with behavioral health needs, psychosocial interventions must be delivered at scale. Despite an increasing effort to implement effective treatments in communities, most individuals with mental health and behavioral problems do not receive EBIs. We posit that organizations that commercialize EBIs play an important role in disseminating EBIs, particularly in the USA. The behavioral health and implementation industry is growing, bringing the implementation field to an important inflection point: how to scale interventions to improve access while maintaining EBI effectiveness and minimizing inequities in access to psychosocial intervention.

Main body

We offer a first-hand examination of five illustrative organizations specializing in EBI implementation: Beck Institute for Cognitive Behavioral Therapy; Incredible Years, Inc.; the PAXIS Institute; PracticeWise, LLC; and Triple P International. We use the Five Stages of Small Business Growth framework to organize themes. We discuss practical structures (e.g., corporate structures, intellectual property agreements, and business models) and considerations that arise when trying to scale EBIs including balancing fidelity and reach of the intervention. Business models consider who will pay for EBI implementation and allow organizations to scale EBIs.

Conclusion

We propose research questions to guide scaling: understanding the level of fidelity needed to maintain efficacy, optimizing training outcomes, and researching business models to enable organizations to scale EBIs.
Clinical efficacy of denosumab, teriparatide, and oral bisphosphonates in the prevention of glucocorticoid-induced osteoporosis: a systematic review and meta-analysis
Authors: Yuan Chuanjian , Liang Yanchen , Zhu Kai , Xie Wenpeng
Published: June 2023

Background

Continuous use of glucocorticoids (GCs) has become the primary cause of secondary osteoporosis. Bisphosphonate drugs were given priority over denosumab and teriparatide in the 2017 American College of Rheumatology (ACR) guidelines but have a series of shortcomings. This study aims to explore the efficacy and safety of teriparatide and denosumab compared with those of oral bisphosphonate drugs.

Methods

We systematically searched studies included in the PubMed, Web of Science, Embase, and Cochrane library databases and included randomized controlled trials that compared denosumab or teriparatide with oral bisphosphonates. Risk estimates were pooled using both fixed and random effects models.

Results

We included 10 studies involving 2923 patients who received GCs for meta-analysis, including two drug base analyses and four sensitivity analyses. Teriparatide and denosumab were superior to bisphosphonates in increasing the bone mineral density (BMD) of the lumbar vertebrae [teriparatide: mean difference [MD] 3.98%, 95% confidence interval [CI] 3.61–4.175%, P = 0.00001; denosumab: MD 2.07%, 95% CI 0.97–3.17%, P = 0.0002]. Teriparatide was superior to bisphosphonates in preventing vertebral fractures and increasing hip BMD [MD 2.39%, 95% CI 1.47–3.32, P < 0.00001]. There was no statistically significant difference between serious adverse events, adverse events, and nonvertebral fracture prevention drugs.

Conclusions

Teriparatide and denosumab exhibited similar or even superior characteristics to bisphosphonates in our study, and we believe that they have the potential to become first-line GC-induced osteoporosis treatments, especially for patients who have previously received other anti-osteoporotic drugs with poor efficacy.
RHAMM regulates MMTV-PyMT-induced lung metastasis by connecting STING-dependent DNA damage sensing to interferon/STAT1 pro-apoptosis signaling
Authors: Tolg Cornelia , Milojevic Maja , Qi Freda W. , Pavanel Hailie A. , Locke M. Elizabeth O. , Ma Jenny , Price Mathew , Nelson Andrew C. , McCarthy James B. , Hill Kathleen A. , Turley Eva A.
Published: June 2023

Background

RHAMM is a multifunctional protein that is upregulated in breast tumors, and the presence of strongly RHAMM+ve cancer cell subsets associates with elevated risk of peripheral metastasis. Experimentally, RHAMM impacts cell cycle progression and cell migration. However, the RHAMM functions that contribute to breast cancer metastasis are poorly understood.

Methods

We interrogated the metastatic functions of RHAMM using a loss-of-function approach by crossing the MMTV-PyMT mouse model of breast cancer susceptibility with Rhamm−/− mice. In vitro analyses of known RHAMM functions were performed using primary tumor cell cultures and MMTV-PyMT cell lines. Somatic mutations were identified using a mouse genotyping array. RNA-seq was performed to identify transcriptome changes resulting from Rhamm-loss, and SiRNA and CRISPR/Cas9 gene editing was used to establish cause and effect of survival mechanisms in vitro.

Results

Rhamm-loss does not alter initiation or growth of MMTV-PyMT-induced primary tumors but unexpectedly increases lung metastasis. Increased metastatic propensity with Rhamm-loss is not associated with obvious alterations in proliferation, epithelial plasticity, migration, invasion or genomic stability. SNV analyses identify positive selection of Rhamm−/− primary tumor clones that are enriched in lung metastases. Rhamm−/− tumor clones are characterized by an increased ability to survive with ROS-mediated DNA damage, which associates with blunted expression of interferon pathway and target genes, particularly those implicated in DNA damage-resistance. Mechanistic analyses show that ablating RHAMM expression in breast tumor cells by siRNA knockdown or CRISPR-Cas9 gene editing blunts interferon signaling activation by STING agonists and reduces STING agonist-induced apoptosis. The metastasis-specific effect of RHAMM expression-loss is linked to microenvironmental factors unique to tumor-bearing lung tissue, notably high ROS and TGFB levels. These factors promote STING-induced apoptosis of RHAMM+ve tumor cells to a significantly greater extent than RHAMM−ve comparators. As predicted by these results, colony size of Wildtype lung metastases is inversely related to RHAMM expression.

Conclusion

RHAMM expression-loss blunts STING-IFN signaling, which offers growth advantages under specific microenvironmental conditions of lung tissue. These results provide mechanistic insight into factors controlling clonal survival/expansion of metastatic colonies and has translational potential for RHAMM expression as a marker of sensitivity to interferon therapy.
6D-QSAR for predicting biological activity of human aldose reductase inhibitors using quasar receptor surface modeling
Authors: Sokouti Babak , Hamzeh-Mivehroud Maryam
Published: June 2023

The application of QSAR analysis dates back a half-century ago and is currently continuously employed in any rational drug design. The multi-dimensional QSAR modeling can be a promising tool for researchers to develop reliable predictive QSAR models for designing novel compounds. In the present work, we studied inhibitors of human aldose reductase (AR) to generate multi-dimensional QSAR models using 3D- and 6D-QSAR methods. For this purpose, Pentacle and Quasar’s programs were used to produce the QSAR models using corresponding dissociation constant (Kd) values. By inspecting the performance metrics of the generated models, we achieved similar results with comparable internal validation statistics. However, considering the externally validated values, 6D-QSAR models provide significantly better prediction of endpoint values. The obtained results suggest that the higher the dimension of the QSAR model, the higher the performance of the generated model. However, more studies are required to verify these outcomes.
A tension spline fitted numerical scheme for singularly perturbed reaction-diffusion problem with negative shift
Authors: Ejere Ababi Hailu , Dinka Tekle Gemechu , Woldaregay Mesfin Mekuria , Duressa Gemechis File
Published: June 2023

Objective

The paper is focused on developing and analyzing a uniformly convergent numerical scheme for a singularly perturbed reaction-diffusion problem with a negative shift. The solution of such problem exhibits strong boundary layers at the two ends of the domain due to the influence of the perturbation parameter, and the term with negative shift causes interior layer. The rapidly changing behavior of the solution in the layers brings significant difficulties in solving the problem analytically. We have treated the problem by proposing a numerical scheme using the implicit Euler method in the temporal direction and a fitted tension spline method in the spatial direction with uniform meshes.

Result

Stability and uniform error estimates are investigated for the developed numerical scheme. The theoretical finding is demonstrated by numerical examples. It is obtained that the developed numerical scheme is uniformly convergent of order one in time and order two in space.
Legionella associated rhabdomyolysis: a case report
Authors: Ma Helena , Bavishi Avni , Jain Bijal
Published: June 2023

Background

Infections have been recognized as an uncommon cause of rhabdomyolysis, with evidence indicating a worse prognosis when compared to rhabdomyolysis caused by other etiologies. Diseases caused byLegionella pneumophilacan present variably, ranging from mild to severe illness, as is sometimes the case with pneumonia. In particular, the triad of Legionnaire’s disease, rhabdomyolysis, and acute kidney injury is associated with a significant increase in the morbidity and mortality, with most patients requiring initiation of renal replacement therapy such as hemodialysis. While the exact mechanism of both the muscle and kidney injury in this setting remains unknown, several hypotheses exist, with some research suggesting multiple yet distinct processes occurring in both target organs.

Case presentation

In this case report, we describe a 53-year-old African American man who presented withLegionella pneumophilapneumonia complicated by rhabdomyolysis and acute kidney injury. He was treated with aggressive fluid resuscitation and a 2-week course of azithromycin. His clinical status improved without necessitating renal replacement therapy or mechanical ventilation. We postulate that early recognition and treatment were key to his recovery. He was discharged 10 days later without recurrence of rhabdomyolysis at the time of this report.

Conclusion

While there are several well-established and more common causes of rhabdomyolysis, clinicians should recognizeLegionella sp.as an etiology, given its association with significant morbidity and mortality.
Identification of novel B cell epitopes in Fiber-2 protein of duck adenovirus 3 and their application
Authors: Lin Yun , Zhang Wenyuan , Xie Jing , Wang Weikang , Xie Quan , Li Tuofan , Shao Hongxia , Qin Aijian , Wan Zhimin , Ye Jianqiang
Published: June 2023

Duck adenovirus 3 (DAdV-3), a newly emerged duck adenovirus, has resulted in significant economic losses to the duck industry across China since 2014. However, little is known about the B cell epitopes in major antigen of DAdV-3 and the serological approach for detection of DAdV-3 is not available. In this study, four monoclonal antibodies (mAbs) specific to Fiber-2 protein of DAdV-3 were first generated and designated as 2G10, 3D9, 5E6, and 6B12. Indirect immunofluorescence assay (IFA) showed that all of the mAbs reacted with the Fiber-2. Moreover, mAbs 2G10, 5E6, and 6B12 demonstrated good activity with Fiber-2 in Western blot. Notably, the Fiber-2 could be immunoprecipitated efficiently by mAb 3D9. Epitope mapping revealed that mAbs 2G10, 3D9, 5E6, and 6B12 recognized 397-429aa, 463-481aa, 67-99aa, and 1-66aa of Fiber-2, respectively. Besides, a novel sandwich ELISA for efficient detection of DAdV-3 was developed based on mAb 3D9 and horseradish peroxidase (HRP) conjugated mAb 3D9. The sandwich ELISA only reacted with DAdV-3 but not with other duck-associated viruses. The limit of detection of the ELISA was 6.25 × 103 TCID50/mL. Overall, the mAbs generated laid the foundation for elucidating the critical role of Fiber-2 in mediating infection and pathogenesis, and the sandwich ELISA approach established here provided efficient and rapid serological diagnostic tool for DAdV-3.
Integrating request replication into FaaS platforms: an experimental evaluation
Authors: Bouizem Yasmina , Dib Djawida , Parlavantzas Nikos , Morin Christine
Published: June 2023

Function-as-a-Service (FaaS) is a popular programming model for building serverless applications, supported by all major cloud providers and many open-source software frameworks. One of the main challenges for FaaS providers is providing fault tolerance for the deployed applications, that is, providing the ability to mask failures of function invocations from clients. The basic fault tolerance approach in current FaaS platforms is automatically retrying function invocations. Although the retry approach is well suited for transient failures, it incurs delays in recovering from other types of failures, such as node crashes. This paper proposes the integration of a Request Replication mechanism in FaaS platforms and describes how this integration was implemented in Fission, a well-known, open-source platform. It provides a detailed experimental comparison of the proposed approach with the retry approach and an Active-Standby approach in terms of performance, availability, and resource consumption under different failure scenarios.
Core components of infection prevention and control programs at the facility level in Kazakhstan: key challenges and opportunities
Authors: Deryabina Anna , Aiypkhanova Ainur , Juvashev Almat , Alimbetov Kuanysh , Tekebayev Kanat , Kassa Getachew , Howard Andrea A.
Published: June 2023

Background

Kazakhstan is developing a National Roadmap to strengthen its Infection Prevention and Control (IPC), but until recently has lacked a country-wide facility-level assessment of IPC performance gaps.

Methods

In 2021, the World Health Organization (WHO)’s IPC Core Components and Minimal Requirements were assessed at 78 randomly selected hospitals across 17 administrative regions using adapted WHO tools. The study included site assessments, followed by structured interviews with 320 hospital staff, validation observations of IPC practices, and document reviews.

Results

All hospitals had at least one dedicated IPC staff member, 76% had IPC staff with any formal IPC training; 95% established an IPC committee and 54% had an annual IPC workplan; 92% had any IPC guidelines; 55% conducted any IPC monitoring in the past 12 months and shared the results with facility staff, but only 9% used monitoring data for improvements; 93% had access to a microbiological laboratory for HAI surveillance, but HAI surveillance with standardized definitions and systematic data collection was conducted in only one hospital. Adequate bed spacing of at least 1 m in all wards was maintained in 35% of hospitals; soap and paper towels were available at the hand hygiene stations in 62% and 38% of hospitals, respectively.

Conclusions

Existing IPC programs, infrastructure, IPC staffing, workload and supplies present within hospitals in Kazakhstan allow for implementation of effective IPC. Development and dissemination of IPC guidelines based on the recommended WHO IPC core components, improved IPC training system, and implementation of systematic monitoring of IPC practices will be important first steps towards implementing targeted IPC improvement plans in facilities.
Development of a digital biomarker and intervention for subclinical depression: study protocol for a longitudinal waitlist control study
Authors: Teepe Gisbert W. , Lukic Yanick X. , Kleim Birgit , Jacobson Nicholas C. , Schneider Fabian , Santhanam Prabhakaran , Fleisch Elgar , Kowatsch Tobias
Published: June 2023

Background

Depression remains a global health problem, with its prevalence rising worldwide. Digital biomarkers are increasingly investigated to initiate and tailor scalable interventions targeting depression. Due to the steady influx of new cases, focusing on treatment alone will not suffice; academics and practitioners need to focus on the prevention of depression (i.e., addressing subclinical depression).

Aim

With our study, we aim to (i) develop digital biomarkers for subclinical symptoms of depression, (ii) develop digital biomarkers for severity of subclinical depression, and (iii) investigate the efficacy of a digital intervention in reducing symptoms and severity of subclinical depression.

Method

Participants will interact with the digital intervention BEDDA consisting of a scripted conversational agent, the slow-paced breathing training Breeze, and actionable advice for different symptoms. The intervention comprises 30 daily interactions to be completed in less than 45 days. We will collect self-reports regarding mood, agitation, anhedonia (proximal outcomes; first objective), self-reports regarding depression severity (primary distal outcome; second and third objective), anxiety severity (secondary distal outcome; second and third objective), stress (secondary distal outcome; second and third objective), voice, and breathing. A subsample of 25% of the participants will use smartwatches to record physiological data (e.g., heart-rate, heart-rate variability), which will be used in the analyses for all three objectives.

Discussion

Digital voice- and breathing-based biomarkers may improve diagnosis, prevention, and care by enabling an unobtrusive and either complementary or alternative assessment to self-reports. Furthermore, our results may advance our understanding of underlying psychophysiological changes in subclinical depression. Our study also provides further evidence regarding the efficacy of standalone digital health interventions to prevent depression.

Trial registration Ethics approval was provided by the Ethics Commission of ETH Zurich (EK-2022-N-31) and the study was registered in the ISRCTN registry (Reference number: ISRCTN38841716, Submission date: 20/08/2022).
Developing and validating an online situational judgment test on the stress coping competence of nursing apprentices
Authors: Warwas Julia , Vorpahl Wiebke , Seeber Susan , Krebs Philine , Weyland Ulrike , Wittmann Eveline , Wilczek Larissa , Strikovic Aldin
Published: June 2023

Converging evidence of high stress levels in the nursing profession as well as their detrimental effects on the execution of nursing actions, quality indicators of care, and self-reported job satisfaction justify the need for test environments that assess stress coping competences in dealing with domain-specific stress factors. Reliable and valid information on the test takers’ stress coping competence can help to identify individual deficits and supportive needs and thus, to design training measures that may contribute to job retention and a skilled workforce. This article describes the development and validation of a digital assessment that ensures authenticity by means of video-based situational judgement tests. Analyses of the performance data were conducted in four steps: (1) the scaling of the data with a partial credit model in order to identify items that are subject to measurement error, (2) differential-item-function analyses for different specializations in nursing education, (3) dimensionality tests, and (4) correlations between test performance and perceived psychological work stress in order to gauge criterion validity. The total sample consisted of n = 300 German nursing apprentices. The results show that the developed test instrument can be used for a reliable and valid measurement of coping skills of (prospective) nurses, covering two essential dimensions. Limitations of the current study and related objectives of future research are discussed together with questions of practical applicability.
A list-mode multi-energy window low-count SPECT reconstruction method for isotopes with multiple emission peaks
Authors: Rahman Md Ashequr , Li Zekun , Yu Zitong , Laforest Richard , Thorek Daniel L. J. , Jha Abhinav K.
Published: June 2023

Background

Single-photon emission computed tomography (SPECT) provides a mechanism to perform absorbed-dose quantification tasks for$$\alpha$$α-particle radiopharmaceutical therapies ($$\alpha$$α-RPTs). However, quantitative SPECT for$$\alpha$$α-RPT is challenging due to the low number of detected counts, the complex emission spectrum, and other image-degrading artifacts. Towards addressing these challenges, we propose a low-count quantitative SPECT reconstruction method for isotopes with multiple emission peaks.

Methods

Given the low-count setting, it is important that the reconstruction method extracts the maximal possible information from each detected photon. Processing data over multiple energy windows and in list-mode (LM) format provide mechanisms to achieve that objective. Towards this goal, we propose a list-mode multi energy window (LM-MEW) ordered-subsets expectation–maximization-based SPECT reconstruction method that uses data from multiple energy windows in LM format and include the energy attribute of each detected photon. For computational efficiency, we developed a multi-GPU-based implementation of this method. The method was evaluated using 2-D SPECT simulation studies in a single-scatter setting conducted in the context of imaging [$$^{223}$$223Ra]RaCl$${_2}$$2, an FDA-approved RPT for metastatic prostate cancer.

Results

The proposed method yielded improved performance on the task of estimating activity uptake within known regions of interest in comparison to approaches that use a single energy window or use binned data. The improved performance was observed in terms of both accuracy and precision and for different sizes of the region of interest.

Conclusions

Results of our studies show that the use of multiple energy windows and processing data in LM format with the proposed LM-MEW method led to improved quantification performance in low-count SPECT of isotopes with multiple emission peaks. These results motivate further development and validation of the LM-MEW method for such imaging applications, including for$$\alpha$$α-RPT SPECT.
Zygoma implant under function: biomechanical principles clarified
Authors: Bedrossian Edmond , Brunski John , Al-Nawas Bilal , Kämmerer Peer W.
Published: June 2023

Purpose

The purpose of this document is to clarify the biomechanical principles involved when zygoma implants are placed under functional loads.

Methods

Two independent reviewers conducted electronic search of the literature from January 2000 to February 2023 describing the biomechanical principles involved using the zygoma implant for maxillary reconstruction. Articles describing the stresses within the zygoma implant, the maxillary bone and the zygoma bone under functional loads were included.

Results

The lack of maxillary boney support at the implant platform resulted in significant higher stress measured within the zygoma implant as well as the zygoma bone.

Conclusion

The maxilla is the primary support when zygoma implants are placed under functional loads. Quad-cortical stabilization of the zygoma implants and their cross-arch stabilization are recommended to reduce the degree of stress whenever possible.
Neuronal autoantibodies in a sample of Egyptian patients with drug-resistant epilepsy
Authors: Mohamed Hadeer , Hemeda Mahmoud , Gaber Ahmed , Zakieldine Hany , Bakr Salwa Ibrahim , Shehab Abeer , Mohamed Nesrine , Talkhan Hala A. , Elshennawy Dina , Rushdy Marwa , Abdelaziz Doaa M. , Masry Yara , Tohamy Ahmed Magdy , El Din Mona Wahid
Published: June 2023

Background

Epilepsy is one of the most common and chronic neurological diseases. About one-third of epilepsy patients do not achieve seizure freedom despite adequate therapy with antiseizure medications (ASMs) and develop drug-resistant epilepsy (DRE). Autoimmunity is increasingly being recognized as a cause of epilepsy in those patients. Some cases are associated with antibodies against several target antigens, including neuronal extracellular proteins as well as intracellular structures. In such patients, immunotherapy may be highly effective. This study aimed to investigate the presence of NMDA-R, AMPA1-R, AMPA2-R, CASPR2, LGI1, GABAB-R, and GAD65 autoantibodies in a sample of Egyptian patients with new-onset DRE; also, to assess the clinical, cerebrospinal fluid (CSF), electroencephalogram (EEG), and radiological characteristics of those patients. Twenty-five patients with recent onset DRE were recruited from the department of Neurology at Ain Shams University (ASU) hospitals. All patients underwent serum and CSF antibody testing using cell-based assay (CBA) at the Immunology unit of the Clinical pathology laboratory at ASU hospitals. This is beside routine CSF analysis, EEG and MRI brain with contrast.

Results

Out of 25 patients with recent onset DRE, one (4%) patient tested positive to anti-NMDA-R antibodies and another one (4%) tested positive to anti-GAD 65 in both serum and CSF. Although the remaining 23 patients tested negative for the 7 autoantibodies, yet 92% of them achieved either seizure freedom or more than 50% reduction in the frequency of seizure and 84% had marked improvement in seizure-associated symptoms after receiving immunotherapy trial. Also, evidence of neuroinflammation was detected in the CSF and MRI brain of the majority of those patients.

Conclusions

Autoimmunity should be considered as a possible etiology of new-onset DRE. It is essential to provide insight into the clinical phenotypes and other associated features of those patients, as there are probably numerous patients who are not positive for one of the available antibodies via clinical laboratory testing. In addition to early diagnosis, early treatment and empirical immunotherapy trial based on the clinical judgment is crucial and is likely to improve outcomes with near-complete seizure freedom.
A systematic review and meta-analysis comparing conservative and surgical treatments for acute patellar dislocation in children and adolescents
Authors: Lee Dong-Yeong , Kang Dong-Geun , Jo Ho-Seung , Heo Se-Joon , Bae Ji-Ho , Hwang Sun-Chul
Published: June 2023

Purpose

This study sought to clarify treatment evidence to treat patellar dislocation by evaluating which treatment could yield better improvement of clinical outcomes for acute patellar dislocation in children and adolescents 18 years of age or younger.

Materials and methods

MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials electronic databases were searched for relevant articles comparing clinical outcomes of conservative and surgical treatments for acute patellar dislocation in children and adolescents published from March 2008 to August 2022. Data searching, extraction, analysis, and quality assessment were performed on the basis of the Cochrane Collaboration guidelines. The quality assessment of each study was investigated using the Physiotherapy Evidence Database (PEDro) critical appraisal scoring system and Newcastle–Ottawa Quality Assessment Scale scores. To calculate the overall combined effect size for each outcome, Review Manager Version 5.3 (The Cochrane Collaboration, Software Update, Oxford) was employed.

Results

Three randomized controlled trials (RCTs) and one prospective study were investigated. In terms of pain [mean difference (MD) 6.59, 95% confidence interval (CI) 1.73–11.45, I2 0%], there were significantly better outcomes in conservative group. Nevertheless, there were no significant differences in any evaluated outcomes such as redislocation [risk ratio (RR) 1.36, 95% CI 0.72–2.54, I2 65%], Kujala score (MD 3.92, 95% CI −0.17 to 8.01, I2 0%), Tegner score (MD 1.04, 95% CI −0.04 to 2.11, I2 71%), or subjective results (RR 0.99, 95% CI 0.74–1.34, I2 33%) between conservative and surgical treatment groups.

Conclusions

Despite better pain outcomes with conservative group, the present study revealed no significant differences in clinical outcomes between conservative treatment and surgical treatment in children and adolescents with acute patellar dislocation. Since there are no significant differences in clinical outcomes between the two groups, routine surgical treatment is not advocated for treating acute patellar dislocation in children and adolescents.
Relationship between galectin-3 level and disease activity in ankylosing spondylitis patients
Authors: Devrimsel Gul , Arpa Medeni , Beyazal Munevver Serdaroglu
Published: June 2023

Background and aims

Ankylosing spondylitis (AS) is a chronic inflammatory disease that chiefly affects the sacroiliac joints and the spine. Galectin-3, a chimera-type member of the galectin family, binds glycoconjugates containing N-acetyllactosamine. Galectins play a role in regulation of embryogenesis, angiogenesis, neurogenesis, and immunity. The aim of the present study was to evaluate the serum galectin-3 level and its possible association with disease activity in AS patients. Forty five AS patients and 35 healthy controls enrolled in this study. All participants with a history of hyperlipidemia, liver, renal, hematological, familial thyroid, neoplastic, autoimmune infectious diseases and using anti-inflammatory drugs were excluded from the study. Serum galectin-3 levels concentration was measured using a commercial chemiluminescent microparticle immunoassay. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were measured. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score–CRP (ASDAS-CRP) were used to evaluate disease activity in AS patients.

Results

Serum galectin-3 levels were significantly higher in AS patients compared to the control group (p = 0.04). A correlation was determined between the serum galectin-3 levels and BASDAI and ASDAS-CRP scores in the AS patients (r = 0.49, p < 0.001; r = 0.56, p < 0.001, respectively). In AS patients, serum galectin-3 levels were significantly related with CRP levels but were not related with ESR (r = 0.57, p < 0.001; r = 0.25, p = 0.09, respectively).

Conclusions

The serum galectin-3 levels were higher in AS patients and were correlated with disease activity. This study may be useful to reveal the role of galectin-3 in inflammation and to evaluate disease activity in AS patients.
Teleconsultation Perceptions of Medical and Radiation Oncologists in the COVID-19 and Post–COVID-19 Era: A National Survey in the Philippines
Authors: Yap Eugene T. , Tan Charmaine L. , Dumago Mark P. , Jacomina Luisa E. , Yu Kelvin Ken L. , Tapispisan Julie Ann R. , Agas Ryan Anthony F. , Co Jayson L. , Bacorro Warren R. , Mejia Michael A. , Sy Ortin Teresa T.
Published: June 2023

PURPOSE

The study reports on the current perception of medical and radiation oncologists regarding teleconsultation in the Philippines. Before the COVID-19 pandemic, the adoption of telemedicine was not widespread. With movement restrictions imposed during the pandemic, physicians were compelled to use telemedicine. It is uncertain whether physicians will still adopt its use in practice in the post–COVID-19 era. This study gives insight into the possible adaptation of this mode of consultation in the future, especially in areas with limited health care resources.

MATERIALS AND METHODS

We conducted a national survey among medical oncologists and radiation oncologists in the Philippines. A 43-item online survey was developed, validated, and administered to the oncologists. The demographics and data from categorical questions were reported as frequencies and percentages.

RESULTS

A total of 142 responses were gathered from 82 medical oncologists and 60 radiation oncologists. There was agreement among participants that, during the pandemic, teleconsultation could be used for the first visit, diagnostic workup request, treatment explanation, follow-up care, and chronic disease management. There was disagreement whether cancer diagnosis disclosure and cancer prognosis revelation could be performed via teleconsultation, and there was agreement that emergency consultation and physical examination would warrant a face-to-face consultation. After the COVID-19 pandemic, 78.7% intend to continue using teleconsultation except for emergency consultations, first visits, physical examination, diagnosis disclosure, and cancer prognosis revelation.

CONCLUSION

Teleconsultation was perceived by oncologists as an acceptable method of providing cancer care during and after the COVID-19 pandemic. Oncologists also intend to use teleconsultation in the post–COVID-19 era in certain aspects of patient care.
AMEERA-3: Randomized Phase II Study of Amcenestrant (Oral Selective Estrogen Receptor Degrader) Versus Standard Endocrine Monotherapy in Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer
Authors: Tolaney Sara M. , Chan Arlene , Petrakova Katarina , Delaloge Suzette , Campone Mario , Iwata Hiroji , Peddi Parvin F. , Kaufman Peter A. , De Kermadec Elisabeth , Liu Qianying , Cohen Patrick , Paux Gautier , Wang Lei , Ternès Nils , Boitier Eric , Im Seock-Ah
Published: June 2023

PURPOSE

Amcenestrant (oral selective estrogen receptor degrader) demonstrated promising safety and efficacy in earlier clinical studies for endocrine-resistant, estrogen receptor–positive/human epidermal growth factor receptor 2–negative (ER+/HER2–) advanced breast cancer (aBC).

PATIENTS AND METHODS

In AMEERA-3 (ClinicalTrials.gov identifier: NCT04059484 ), an open-label, worldwide phase II trial, patients with ER+/HER2– aBC who progressed in the (neo)adjuvant or advanced settings after not more than two previous lines of endocrine therapy (ET) were randomly assigned 1:1 to amcenestrant or single-agent endocrine treatment of physician's choice (TPC), stratified by the presence/absence of visceral metastases, previous/no treatment with cyclin-dependent kinase 4/6 inhibitor, and Eastern Cooperative Oncology Group performance status (0/1). The primary end point was progression-free survival (PFS) by independent central review, compared using a stratified log-rank test (one-sided type I error rate of 2.5%).

RESULTS

Between October 22, 2019, and February 15, 2021, 290 patients were randomly assigned to amcenestrant (n = 143) or TPC (n = 147). PFS was numerically similar between amcenestrant and TPC (median PFS [mPFS], 3.6 v 3.7 months; stratified hazard ratio [HR], 1.051 [95% CI, 0.789 to 1.4]; one-sided P = .643). Among patients with baseline mutated ESR1; (n = 120 of 280), amcenestrant numerically prolonged PFS versus TPC (mPFS, 3.7 v 2.0 months; stratified HR, 0.9 [95% CI, 0.565 to 1.435]). Overall survival data were immature but numerically similar between groups (HR, 0.913; 95% CI, 0.595 to 1.403). In amcenestrant versus TPC groups, treatment-emergent adverse events (any grade) occurred in 82.5% versus 76.2% of patients and grade ≥3 events occurred in 21.7% versus 15.6%.

CONCLUSION

AMEERA-3 did not meet its primary objective of improved PFS with amcenestrant versus TPC although a numerical improvement in PFS was observed in patients with baseline ESR1 mutation. Efficacy and safety with amcenestrant were consistent with the standard of care for second-/third-line ET for ER+/HER2– aBC.