bluuebunny/crossref_metadata_2025 huggingface dataset:
Finding a rhythm: The mediality of researching digital skill as process
Authors: Lesage Frederik , Stewart Nicole K , Tang Song
Published: August 2023

Our objective for this article is to illustrate the importance of understanding digital skill as process by taking its mediality—interweaving tools, technologies, and media—into consideration. Drawing on 12 case studies with participants performing digital tasks, we use Ingold’s four phases of skill (getting ready, setting out, carrying on, and finishing off) to research and represent the rhythm of digital skill. By using medialities of inscription, scripting, and annotation, we demonstrate how researchers can use mediality to perceive rhythms of digital skill without being physically co-located in the performance. As different medialities enable and constrain the perception and descriptions of digital skill, we develop spotlines as a method that combines different medialities particularly well suited for describing and comparing the temporal order of phases for performing digital skill by rendering each performer’s pace and intensity.
Using shot peening and burnishing to improve fatigue performance of additively manufactured 316L stainless steel
Authors: Sayadi Daniyal , Rangrizian Hossein , Khodabandeh Alireza , Nezarati Masoud , Hemasian Etefagh Ardeshir , Khajehzadeh Mohsen , Razfar Mohammad Reza
Published: August 2023

Despite the growing demands for personalized items, the capacity of conventional production techniques is restricted to respond to such needs. Instead of conventional manufacturing processes, the intended structure can be directly constructed in a layer-by-layer manner, also known as additive manufacturing (AM). Among AM methods, selective laser melting (SLM) has gained a great deal of attention due to its low cost and availability. However, the poor surface quality in this method is still a problem as it may influence critical mechanical properties of the components like their fatigue life. Therefore, adequate postprocesses are required for additively manufactured metals. In the present study, shot peening (SP) and burnishing were applied as postprocesses to the 316 L stainless steel manufactured by SLM, and then, surface roughness, porosity, microhardness, and fatigue performance were experimentally investigated. Based on the results, the mean surface roughness (Ra) of the as-SLMed sample was 10.907 µm which decreased to 8.543 and 1.324 µm, after SP and the burnishing processes, respectively. Interestingly, the burnishing process was more effective in eliminating near-surface pores and improving microhardness of the samples compared to SP. In addition, the fatigue life of the as-SLMed sample (135,000 cycles) slightly improved after SP (353,000 cycles), while burnishing drastically enhanced the fatigue life of the samples (3,030,000 cycles).
The William Houston gold medal of the Royal College of Surgeons of Edinburgh 2022: Two case reports
Authors: Leck Richard
Published: August 2023

This paper describes the orthodontic treatment of two cases that were successful in winning the William Houston Gold Medal at the Membership in Orthodontics Examinations of the Royal College of Surgeons of Edinburgh in 2022. Both cases discuss the management of palatally impacted maxillary canines and treatment was initiated during the emerging COVID-19 crisis and completed over a 27-month period. The first case describes the management of a 15-year-old female with a Class II division 1 incisor relationship complicated by a palatally impacted upper left canine, moderate upper and lower arch crowding, and a lower centreline discrepancy with an associated right lateral displacement on closure. Treatment involved open surgical exposure of the impacted canine, a quad helix appliance, premolar extractions, and upper and lower fixed appliances. The second case describes the management of a 14-year-old female with a Class III incisor relationship complicated by bilaterally impacted maxillary canines, impeded eruption of the lower right second molar, moderate lower and severe upper arch crowding, and an upper centreline discrepancy. These case reports aim to demonstrate the high standards of care achieved by Orthodontic Specialty Trainee Registrars in the UK and provide aspirational standards for future trainees.
Shifts in Facial Impression Structures Across Group Boundaries
Authors: Hong Youngki , Freeman Jonathan B.
Published: August 2023

Facial impressions have long been argued to be driven by two independent dimensions of trustworthiness and dominance. However, in an intergroup context, we reasoned that these dimensions may shift predictably and become more positively related for ingroup members, yet negatively related for outgroup members, due to dominance signaling outgroup threat and/or ingroup prosociality. In two studies, we examined how the two dimensions shift across minimal group boundaries for White targets. In Study 1, core dimensions of trustworthiness and dominance became intertwined with each other differently for ingroup and outgroup targets. In Study 2, stronger stereotypic beliefs that trustworthiness ≈ dominance for ingroup than outgroup mediated the shifts in facial impression dimensions. This work advances our understanding of facial impressions and intergroup bias by showing that the facial impression dimensions are not fixed but may shift across group boundaries and that such shifts occur above and beyond simple ingroup favoritism.
Responses to concerns raised about publications don’t address the concerns raised
Authors: Bolland Mark J , Avenell Alison , Grey Andrew
Published: August 2023

Recently in the Journal, Amanda Williams described her experience of raising concerns about a group of trials with “untrustworthy data”. We were inspired by the work of Williams and colleagues to examine these and other trials by the same research group. Similar to Williams, we found that the patterns of reported data differed from the patterns expected to arise from valid randomisation. We also identified a high proportion of reported baseline p-values for categorial variables that differed from independently calculated p-values. We reported these findings to the affected journals but none of the concerns were addressed and no action will be taken about the majority. Despite the large number of unresolved concerns about these trials, readers will be unaware of the issues, which seems entirely unsatisfactory.
Case report: Monoclonal antibodies as an alternative treatment for new daily persistent headache
Authors: Bancalari Ernesto M , Hernández Natalia , Soria Analia , Bruera Osvaldo
Published: August 2023

Background:

New Daily Persistent Headache (NDPH) is a disabling daily headache that causes huge frustration for patients and headache specialists. Elevated TNF-alpha levels, that elevate CGRP levels, on the CSF of NDPH patients has been described as a possible cause of this disease. TNF-alpha inhibitors like doxycycline, venlafaxine, montelukast and lithium have been used in the past to treat NDPH patients, with relatively good success as described from case reports.

Conclusion:

We report three NDPH patients that improved with the administration of Anti CGRP monoclonal antibodies (mAbs), after trying multiple treatments. We propose this class of drugs, as a therapeutic option for NDPH.
Do physicians remember cases? Implications for longitudinal designs in medical research and competency assessment
Authors: Brunyé Tad T , Konold Catherine E , Wang Jason , Kerr Kathleen F , Drew Trafton , Shucard Hannah , Soroka Kim , Weaver Donald L , Elmore Joann G
Published: August 2023

Background

In pathology and other specialties of diagnostic medicine, longitudinal studies and competency assessments often involve physicians interpreting the same images multiple times. In these designs, a washout period is used to reduce the chances that later interpretations are influenced by prior exposure.

Objective/s

The present study examines whether a washout period between 9 and 39 months is sufficient to prevent three effects of prior exposure when pathologists review digital breast tissue biopsies and render diagnostic decisions: faster case review durations, higher confidence, and lower perceived difficulty.

Methods

In a longitudinal breast pathology study, 48 resident pathologists reviewed a mix of five novel and five repeated digital whole slide images during Phase 2, occurring 9–39 months after an initial Phase 1 review. Importantly, cases that were repeated for some participants in Phase 2 were novel for other participants in Phase 2. We statistically tested for differences in participants’ case review duration, self-reported confidence, and self-reported difficulty in Phase 2 based on whether the case was novel or repeated.

Results

No statistically significant difference in review time, confidence, or difficulty as a function of whether the case was repeated or novel in a Phase 2 review occurring 9-39 months after initial viewing; this same result was found in a subset of participants with a shorter (9-14-months) washout.

Conclusion

These results provide evidence to support the efficacy of at least a 9-months washout period in the design of longitudinal medical imaging and informatics studies to ensure no detectable effect of initial exposure on participant’s subsequent case review.
Magnetically controlled graphene field-effect transistor biosensor for highly sensitive detection of cardiac troponin I
Authors: Zhu Xiaofeng , Cheng Kangning , Ding Yue , Liu Huanqing , Xie Shuqi , Cao Yuwei , Yue Weiwei
Published: August 2023

Herein, we have constructed a magnetic graphene field-effect transistor biosensor (MGFETs) for highly sensitive detection of cardiac troponin I (CTNI). Graphene films transferred to ITO conductive glass as conductive channels. CTNI aptamer was immobilized onto the graphene film via 1-pyrene-butanoic acid succinimidyl ester (PBASE) to capture CTNI. Magnetic nanobeads (MBs) modified with CTNI antibody were added to the reaction chamber to form an aptamer/CTNI/antibody/magnetic nanobeads sandwich-type complex. We found that the magnetic force exerted on the complex leads to an impedance change of the graphene film. The reason for this result is that the magnetic field exerts an influence on the MBs, causing CTNI aptamer strand to bend, resulting in a change in the distance between the double conductive layers of the graphene film surface and the test solution. With periodic sampling integration, different concentrations of CTNI can be detected with high sensitivity. Due to the stringent recognition capability and high affinity between the CTNI aptamer and CTNI, MGFETs have the potential to detect various types of proteins. Furthermore, MGFETs also have the potential to be utilized for the detection of DNA or specific cells in the future.
A knowledge graph approach to predict and interpret disease-causing gene interactions
Authors: Renaux Alexandre , Terwagne Chloé , Cochez Michael , Tiddi Ilaria , Nowé Ann , Lenaerts Tom
Published: August 2023

Background

Understanding the impact of gene interactions on disease phenotypes is increasingly recognised as a crucial aspect of genetic disease research. This trend is reflected by the growing amount of clinical research on oligogenic diseases, where disease manifestations are influenced by combinations of variants on a few specific genes. Although statistical machine-learning methods have been developed to identify relevant genetic variant or gene combinations associated with oligogenic diseases, they rely on abstract features and black-box models, posing challenges to interpretability for medical experts and impeding their ability to comprehend and validate predictions. In this work, we present a novel, interpretable predictive approach based on a knowledge graph that not only provides accurate predictions of disease-causing gene interactions but also offers explanations for these results.

Results

We introduce BOCK, a knowledge graph constructed to explore disease-causing genetic interactions, integrating curated information on oligogenic diseases from clinical cases with relevant biomedical networks and ontologies. Using this graph, we developed a novel predictive framework based on heterogenous paths connecting gene pairs. This method trains an interpretable decision set model that not only accurately predicts pathogenic gene interactions, but also unveils the patterns associated with these diseases. A unique aspect of our approach is its ability to offer, along with each positive prediction, explanations in the form of subgraphs, revealing the specific entities and relationships that led to each pathogenic prediction.

Conclusion

Our method, built with interpretability in mind, leverages heterogenous path information in knowledge graphs to predict pathogenic gene interactions and generate meaningful explanations. This not only broadens our understanding of the molecular mechanisms underlying oligogenic diseases, but also presents a novel application of knowledge graphs in creating more transparent and insightful predictors for genetic research.
Expression profile and bioinformatics analysis of circRNA and its associated ceRNA networks in longissimus dorsi from Lufeng cattle and Leiqiong cattle
Authors: Yang Chuang , Wu Longfei , Guo Yongqing , Li Yaokun , Deng Ming , Liu Dewu , Liu Guangbin , Sun Baoli
Published: August 2023

This paper aims to explore the role of circRNA expression profiles and circRNA-associated ceRNA networks in the regulation of myogenesis in the longissimus dorsi of cattle breeds surviving under subtropical conditions in southern China by RNA sequencing and bioinformatics analysis. It also aims to provide comprehensive understanding of the differences in muscle fibers in subtropical cattle breeds and to expand the knowledge of the molecular networks that regulate myogenesis. With regard to meat quality indicators, results showed that the longissimus dorsi of LQC had lower pH (P < 0.0001), lower redness (P < 0.01), lower shear force (P < 0.05), and higher brightness (P < 0.05) than the longissimus dorsi of LFC. With regard to muscle fiber characteristics, the longissimus dorsi of LQC had a smaller diameter (P < 0.0001) and higher density of muscle fibers (P < 0.05). The analysis results show that the function of many circRNA-targeted mRNAs was related to myogenesis and metabolic regulation. Furthermore, in the analysis of the function of circRNA source genes, we hypothesized that btacirc_00497 and btacirc_034497 may regulate the function and type of myofibrils by affecting the expression of MYH6, MYH7, and NEB through competitive linear splicing.
Microbiota-derived short chain fatty acids in fermented Kidachi Aloe promote antimicrobial, anticancer, and immunomodulatory activities
Authors: Al-Madboly Lamiaa A. , Yagi Akira , Kabbash Amal , El-Aasr Mona A. , El-Morsi Rasha M.
Published: August 2023

Background

Fermented Aloe leaf juice is a commonly used food supplement in Japan. In a previous study, fermentation ofA. arborescencejuice was performed and the presence of short-chain fatty acids (SCFAs) was confirmed and quantified. Samples were collected before and after the fermentation process to be subjected, in the present study, to DNA extraction, 16S rRNA gene (V3–V4 regions) amplification, and sequencing by the next-generation Illumina MiSeq sequencer. Our work aims to analyze the sequences to assess the bacterial diversity in the juice before and after fermentation, identify the beneficial microbes responsible for the production of SCFAs, and evaluate some of the biological activities of the fermented juice.

Results

Data revealed the richness and diversity of the bacterial community in the fermented juice compared to the unfermented control. Relative abundance of bacterial phyla showed that the majority of the microbial community in the test samples corresponded toPseudomonadota(unfermented; 10.4%, fermented; 76.36%), followed by Bacillota (unfermented; 4.71%, fermented; 17.13%) and thenBacteroidota(unfermented; 0.57%, fermented; 1.64%). For the fermented sample, 84% of Bacillota were lactobacilli. A hierarchically clustered heatmap revealed thatLactobacilluswas the most abundant genus in both samples suggesting its involvement in the production of SCFAs.

To assess potential health benefits, the anticancer efficacy of the fermented product ofA. arborescenswas investigated against colorectal cancer (IC50 = 3.5 µg/ml) and liver cancer (IC50 = 6.367 µg/ml) compared to the normal peripheral blood mononuclear cells (PBMCs). Flow cytometric analysis of the cell cycle pattern revealed remarkable population arrest in G0 and G1, however, the highest percentages were mainly in the G1 phase for Hep-G2 (40.1%) and HCT-116 (53.2%) cell lines. This effect was accompanied by early apoptotic profiles of HCT-116 (36.9%) and late apoptosis for Hep-G2 (17.3%). Furthermore, immunomodulatory properties demonstrated a significantly (p < 0.001) reduced percentage of induced TNF-α while enhancing IFN-γ dramatically. For antimicrobial activities, marked broad-spectrum activities were recorded against some bacterial and fungal pathogens (17–37 mm inhibition zone diameter range).

Conclusion

Therefore, this study affords the basis of bacterial community composition in fermentedA. arborescensjuice as well as its potential biological benefits.
Randomized comparison of effects of two different remifentanil dose on surgical conditions during endoscopic sinus surgery
Authors: Jeong JinHyeok , Park ChanWoo , Yoon YoungJoon , Lee DoJae , Cho SangYun
Published: August 2023

Background

The combination of propofol and remifentanil results in better surgical field conditions during endoscopic sinus surgery than inhalation anesthesia. This study compared surgical field conditions between two groups receiving low or high concentration of remifentanil and hemodynamic variables using non-invasive cardiac monitoring.

Methods

Fifty-four patients between ASA I or II, were randomly assigned to either the high-concentration remifentanil group (HR), effect-site concentration of 8 ng/mL or the low-concentration remifentanil group(LR), effect-site concentration of 4 ng/mL. Surgical condition was evaluated using the Boezaart Surgical Field Grading Scale presented by Boezaart. Cardiac output was measured using non-invasive cardiac monitoring (CSN-1901).

Results

In terms of surgical conditions, the HR group showed significantly lower values than the LR group (p = 0.021) at 90 min after the start of surgery. Heart rate was significantly lower in the HR group than the LR group at 30, 60, and 90 min after the start of surgery (30 min; p = 0.005, 60 min; p = 0.002, 90 min; p = 0.001). There was a statistically significant decrease of cardiac output in the HR group compared to the LR group immediately after endotracheal intubation and at 30, 60, and 90 min after the start of surgery (Base; P = 0.222, Intubation; P = 0.016, 30 min; p = 0.014, 60 min; P = 0.012, 90 min; P = 0.008). However, in the case of stroke volume, there was no significant difference between the two groups in all measurements.

Conclusion

When comparing the HR group and the LR group, the surgical condition was improved at 90 min after the start of surgery. MAP was lower in the HR group and this was a result of reduction in cardiac output primarily attributed to the decrease in heart rate rather than a decrease in stroke volume.

Trial registration

Clinical Trial Registry of the Republic of Korea (KCT0006453).
Medical care and biomarker-based assessment of mortality in two cohorts of patients with chronic coronary syndrome 10 years apart
Authors: Rehm Martin , Jaensch Andrea , Schöttker Ben , Mons Ute , Hahmann Harry , Koenig Wolfgang , Brenner Hermann , Rothenbacher Dietrich
Published: August 2023

Background

This study aimed to describe the characteristics and mortality of two cohorts of patients with chronic coronary syndrome (CCS) recruited with identical study designs in the same rehabilitation clinics but approximately 10 years apart.

Methods

The KAROLA cohorts included patients with CCS participating in an inpatient cardiac rehabilitation programme in Germany (KAROLA-I: years 1999/2000, KAROLA-II: 2009–2011). Blood samples and information on sociodemographic factors, lifestyle, and medical treatment were collected at baseline, at the end of rehabilitation, and after one year of follow-up. A biomarker-based risk model (ABC-CHD model) and Cox regression analysis were used to evaluate cardiovascular (CV) and non-CV mortality risk.

Results

We included 1130 patients from KAROLA-I (mean age 58.7 years, 84.4% men) and 860 from KAROLA-II (mean age 60.4 years, 83.4% men). Patients in the KAROLA-I cohort had significantly higher concentrations of CV biomarkers and fewer patients were taking CV medications, except for statins. The biomarker-based ABC-CHD model provided a higher estimate of CV death risk for patients in the KAROLA-I cohort (median 3-year risk, 3.8%) than for patients in the KAROLA-II cohort (median 3-year risk, 2.7%, p-value for difference < 0.001). After 10 years of follow-up, 91 (8.1%) patients in KAROLA-I and 45 (5.2%) in KAROLA-II had died from a CV event.

Conclusions

Advances in disease management over the past 20 years may have led to modest improvements in pharmacological treatment during cardiac rehabilitation and long-term outpatient care for patients with CCS. However, modifiable risk factors such as obesity have increased in the more recent cohort and should be targeted to further improve the prognosis of these patients.
An innovative sequential mixed-methods approach to evaluating clinician acceptability during implementation of a standardized labor induction protocol
Authors: Hamm Rebecca Feldman , Levine Lisa D. , Szymczak Julia E. , Parry Samuel , Srinivas Sindhu K. , Beidas Rinad S.
Published: August 2023

Background

Implementation outcomes, including acceptability, are of critical importance in both implementation research and practice. The gold standard measure of acceptability, Acceptability of Intervention Measure (AIM), skews positively with a limited range. In an ongoing hybrid effectiveness-implementation trial, we aimed to evaluate clinician acceptability of induction standardization. Here, we describe an innovative mixed-methods approach to maximize the interpretability of the AIM using a case study in maternal health.

Methods

In this explanatory sequential mixed methods study, we distributed the validated, 4-question AIM (total 4–20) to labor and delivery clinicians 6 months post-implementation at 2 sites (Site 1: 3/2021; Site 2: 6/2021). Respondents were grouped by total score into tertiles. The top (“High” Acceptability) and bottom (“Low” Acceptability) tertiles were invited to participate in a 30-minute semi-structured qualitative interview from 6/2021 to 10/2021 until thematic saturation was reached in each acceptability group. Participants were purposively sampled by role and site. Interviews were coded using an integrated approach, incorporating a priori attributes (Consolidated Framework for Implementation Research constructs) into a modified content analysis approach.

Results

104 clinicians completed the initial survey; 24 were interviewed (12 “High” and 12 “Low” Acceptability). Median total AIM scores were 20/20 IQR[20–20] in the High and 12.5/20 IQR[11–14] in the Low Acceptability groups. In both groups, clinicians were enthusiastic about efforts to standardize labor induction, believing it reduces inter-clinician variability and improves equitable, evidence-based care. In the Low Acceptability group, clinicians stated the need for flexibility and consideration for patient uniqueness. Rarely, clinicians felt labor induction could not or should not be standardized, citing discomfort with medicalization of labor, and concerns with “bulldozing” the patient with interventions. Suggested strategies for overcoming negative sentiment included comprehensive clinician education, as well as involving patients as active participants in the protocol prenatally.

Conclusions

This study utilized AIM in an innovative sequential mixed-methods approach to characterize clinician acceptability, which may be generalizable across implementation endeavors. By performing this work during a hybrid trial, implementation strategies to improve acceptability emerged (clinician education focusing on respect for flexibility; involving patients as active participants prenatally) for year 2, which will inform future multi-site work.
Link between the referring physician and breast and cervical cancers screening: a cross-sectional study in France
Authors: Ouanhnon Lisa , Bugat Marie-Eve Rouge , Druel Vladimir , Grosclaude Pascale , Delpierre Cyrille
Published: August 2023

Background

The aims of the “médecin traitant” or referring physician (RP) reform, introduced in France in 2004, were to improve the organisation and quality of care and to allow for greater equity, particularly in terms of prevention. The objective of our study was to evaluate the effect of having a declared RP on the uptake of screening for breast and cervical cancers, and to explore the mechanisms involved.

Methods

We used an existing dataset of 1,072,289 women, which combines data from the Health Insurance information systems, with census data. We built multivariable logistic regression models to study the effect of having a RP on the uptake of mammography and pap smear, adjusted for age, socio-economic level, health status and healthcare provision. We secondarily added to this model the variable “having consulted a General Practitioner (GP) within the year”. Finally, we evaluated the interaction between the effect of having a referring physician and the area of residence (metropolitan/urban/rural).

Results

Patients who had a declared RP had a significantly higher uptake of mammography and pap smear than those who did not. The strength of the association was particularly important in very urban areas. The effect of having visited a GP seemed to explain a part of the correlation between having a RP and uptake of screening.

Conclusions

Lower rates of gynaecological screening among women without an RP compared to those with an RP may partly reflect a specific behaviour pattern in women less adherent to the health care system. However, this result also shows the importance of the RP, who assumes the key role of relaying public health information in a more personalised and adapted way.
Burden in caregivers of primary care patients with dementia: influence of neuropsychiatric symptoms according to disease stage (NeDEM project)
Authors: García-Martín Victoria , de Hoyos-Alonso M Canto , Delgado-Puebla Rosalía , Ariza-Cardiel Gloria , del Cura-González Isabel
Published: August 2023

Background

Caregiver burden is related to personal factors and patient characteristics and is greater when neuropsychiatric symptoms (NPSs) are present. Objective: Estimate the prevalence of burden among caregivers of dementia patients and its association with NPSs and identify NPSs causing greater caregiver distress according to dementia stage.

Methods

A cross-sectional observational study in caregivers of noninstitutionalized dementia patients was conducted. Caregiver variables were sociodemographic, time of care, NPS-associated distress based on the Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D) and burden based on the Zarit Burden Interview (ZBI). Patient variables were time since disease onset, Global Deterioration Scale (GDS) disease stage, functional assessment and NPS presence and intensity according to the Neuropsychiatric Inventory (NPI). The mean ZBI score, prevalence of burden and NPI-D score with 95% CIs at each dementia stage were estimated. Factors associated with burden were identified by multivariate analysis.

Results

Of the 125 caregivers included, 77.6% were women, with a mean age of 60.7 (± 14.3) years; 78.4% (95%CI: 71.0; 86.0) experienced burden. The mean ZBI score was 12.3 (95%CI: 11.6; 12.9) and increased according to NPS number (p = 0.042). The NPSs causing the most burden were disinhibition (93.5%), irritability (87.3%) and agitation (86.1%). Agitation, apathy, and sleep disorders were the NPSs generating the greatest overall caregiver distress; depression (max NPI-D 1.9), hyperactivity (max NPI-D 2.1), and psychosis symptoms (max NPI-D 1.6) generated the greatest distress at stage GDS 3, stages GDS 4–5, and stages GDS 6–7, respectively. The NPI score (OR = 1.0, 95%CI 1.0; 1.1), intensity of irritability (OR = 1.2, 95%CI 1.0; 1.6), disinhibition (OR = 2.6, 95%CI 1.1; 5.8) and hyperactivity subsyndrome (OR = 1.1, 95%CI 1.0; 1.2) were associated with caregiver burden. Other associated factors were female gender (OR = 6.0, 95%CI 1.6; 22.8), ≥ 8 h daily care (OR = 5.6, 95%CI 1.4; 22.8), working outside the home (OR = 7.6, 95%CI 1.8; 31.8), living with the patient (OR = 4.5, 95%CI 1.1; 19.6), kinship (OR = 5.4, 95%CI 1.0; 28.2) and lower patient education (OR = 8.3, 95%CI 2.3; 30.3).

Conclusions

The burden on caregivers of dementia patients is high and associated with NPS presence and intensity. Disinhibition and irritability caused the highest burden. Depression, hyperactivity and psychosis produce more distress in mild, mild-moderate and severe dementia, respectively.
The effect of follow-up blood cultures on mortality and antibiotic use in gram-negative bloodstream infections
Authors: Yildiz Mehmet , Habibi Hamid , Altin Fatma Betul , Corbacioglu Seref Kerem , Ozger Hasan Selcuk
Published: August 2023

Background

Gram-negative bloodstream infections (GN-BSIs) are a significant clinical challenge. The utility of follow-up blood cultures (FUBCs) in GN-BSIs and their impact on mortality and antibiotic consumption are areas of debate. This study aimed to evaluate the effect of FUBCs on mortality and antibiotic consumption in patients with GN-BSIs.

Methods

This single-center, retrospective study was conducted in aged > 18 years of patients with GN-BSIs. FUBC was defined as a blood culture performed 2–7 days after the first blood culture. Patients were grouped as FUBC and no FUBC and compared. A 1:1 match analysis was performed between the groups according to the SOFA score. The matched subgroup was compared for mortality risk factors with logistic regression models. The two groups were compared for the duration of effective antibiotic therapy and total antibiotic consumption (days of therapy per 1000 patient days (DOT/1000 PD)).

Results

FUBC was performed in 564 (69.4%) of 812 patients. Persistent, positive and negative FUBC rates were 7.9%, 14%, and 78%, respectively. The frequency of persistent GN-BSI in patients with appropriate antibiotic therapy was 3.9%. SOFA score (OR:1.33; 95% CI, 1.23–1.44), Charlson comorbidity index score (OR:1.18; 95% CI, 1.08–1.28), hospital-acquired infections (OR:1.93; 95% CI, 1.08–3.46) and carbapenem-resistant GN-BSI (OR: 2.92; 95% CI, 1.72–4.96) were independent risk factors for mortality. No relationship was found between FUBC and mortality (p > 0.05). Duration of effective antibiotic therapy (10(4–16) vs. 15(9–20), p < 0.001) and DOT/1000 PD (1609 (1000–2178) vs. 2000 (1294–2769), p < 0.001) were longer in the FUBC group.

Conclusion

Routine FUBC should not be recommended because of the low prevalence of persistent infections in patients under appropriate antibiotic therapy and FUBC increases antibiotic consumption.
Comparative study of diagnostic efficacy of sputum and bronchoalveolar lavage fluid specimens in community-acquired pneumonia children treated with fiberoptic bronchoscopy
Authors: Wang Le , Lu Sukun , Guo Yinghui , Liu Jianhua , Wu Peng , Yang Shuo
Published: August 2023

Background

Community-acquired pneumonia (CAP) is usually diagnosed in children, and the type of respiratory specimen is critical. Differences in pathogens detection between induced sputum (IS) and bronchoalveolar lavage fluid (BALF) have not been evaluated.

Methods

In 2018, paired sputum and BALF samples from CAP hospitalised children with indications for bronchoalveolar lavage (BAL) were subjected to multiplex PCR for the detection of 11 common respiratory pathogens.

Results

A total of 142 children with paired sputum and BALF were tested. The overall positivity rate was 85.9% (122/142) for sputum and 80.3% (114/142) for BALF. The two specimens presented almost perfect agreement between the detection on M. pneumoniae, influenza A, influenza B, bocavirus and RSV. In contrast, adenovirus had the lowest kappa value of 0.156, and a false negative rate (FNR) of 66.7%. Rhinovirus had the highest false positive rate (FPR) as 18.5%. The consistent rate was significantly higher in school-age children than those under 1 year old (p = .005). Bacterial co-infection in BALF specimens were observed in 14.8% (21/142). Of the 11 discordant pairs of specimens, 9 cases were sputum(+)/BALF(-) with adenovirus predominating.

Conclusion

Our findings suggest that the consistency of results between sputum and BALF is pathogen specific. Careful consideration needs to be given to whether sputum can be used as a substitute for BALF when children are young or co-infections with bacteria are suspected.
Molecular investigations of Mycobacterium tuberculosis genotypes among baseline and follow-up strains circulating in four regions of Eswatini
Authors: Dlamini Talent C. , Mkhize Brenda T. , Sydney Clive , Maningi Nontuthuko E. , Malinga Lesibana A.
Published: August 2023

Background

The tuberculosis (TB) epidemic remains a major global health problem and Eswatini is not excluded. Our study investigated the circulating genotypes in Eswatini and compared them at baseline (start of treatment) and follow-up during TB treatment.

Methods

Three hundred and ninety (n = 390) participants were prospectively enrolled from referral clinics and patients who met the inclusion criteria, were included in the study. A total of 103 participants provided specimens at baseline and follow-up within six months. Mycobacterium tuberculosis (M.tb) strains were detected by GeneXpert® MTB/RIF assay (Cephied, USA) and Ziehl -Neelsen (ZN) microscopy respectively at baseline and follow-up time-points respectively. The 206 collected specimens were decontaminated and cultured on BACTEC™ MGIT™ 960 Mycobacteria Culture System (Becton Dickinson, USA). Drug sensitivity testing was performed at both baseline and follow-up time points. Spoligotyping was performed on both baseline and follow-up strains after DNA extraction.

Results

Resistance to at least one first line drug was detected higher at baseline compared to follow-up specimens with most of them developing into multidrug-resistant (MDR)-TB. A total of four lineages and twenty genotypes were detected. The distribution of the lineages varied among the different regions in Eswatini. The Euro-American lineage was the most prevalent with 46.12% (95/206) followed by the East Asian with 24.27% (50/206); Indo-Oceanic at 9.71% (20/206) and Central Asian at 1.94% (4/206). Furthermore, a high proportion of the Beijing genotype at 24.27% (50/206) and S genotype at 16.50% (34/206) were detected. The Beijing genotype was predominant in follow-up specimens collected from the Manzini region with 48.9% (23/47) (p = 0.001). A significant proportion of follow-up specimens developed MDR-TB (p = 0.001) with Beijing being the major genotype in most follow-up specimens (p < 0.000).

Conclusion

Eswatini has a high M.tb genotypic diversity. A significant proportion of the TB infected participants had the Beijing genotype associated with MDR-TB in follow-up specimens and thus indicate community wide transmission.
Primary lateral sclerosis plus parkinsonism: a case report
Authors: Moturu Abhaya , Welch Wade
Published: August 2023

Background

The standard of diagnosing primary lateral sclerosis, the Pringle criteria, requires three years of purely upper motor neuron symptom presentation before confirming diagnosis. This classic standard has been questioned on occasion due to its restrictive range of both time period and symptomatic exhibition.

Case presentation

This case report will review a 57-year-old Caucasian female who presented with pyramidal and extrapyramidal features suggestive of the exceedingly rare disease primary lateral sclerosis plus parkinsonism. We will describe the mixture of upper motor neuron signs and striking parkinsonian symptoms experienced by the patient, as well as the full diagnostic workup leading to her preliminary diagnosis. The details of this case will then be utilized to explore the diagnostic criteria of primary lateral sclerosis, as well as to work through the differential of conditions resembling Parkinson’s disease.

Conclusions

The current criteria to diagnose primary lateral sclerosis may be excluding patients with the disease and is an ongoing area of investigation. A thorough differential including other neurodegenerative conditions is necessary to consider and requires long-term follow-up.
Circ_0021350 plays an oncogene role by regulating miR-1207-3p/PIK3R3 in glioblastoma
Authors: Tan Cheng , Wei Jun , Li Zhaohui , Tian Nan , Wang Zhengming , Wang Guan , Han Liang , Tian Yu
Published: August 2023

Background

Glioblastoma (GBM) is the most malignant glioma, with poor survival rates and prognosis. Several studies have reported the abnormal expression of circular RNAs (circRNAs) and their functions in the malignant biological behavior of GBM. However, such research is still in the preliminary stages, and further study is needed to confirm the therapeutic potential of circRNAs in GBM.

Methods

RNA-seq was performed using four tumor tissues from patients with GBM and their adjacent non-tumor brain tissues to screen differentially expressed circRNAs. Fluorescence in situ hybridization assay was used to examine the location of circ_0021350 in glioma cells. In addition, a series of biological function assays were employed to verify the oncogenic role of circ_0021350 in GBM. Quantitative reverse transcription PCR was used to examine circular, micro- (miRNA), and messenger RNA (mRNA) levels. Furthermore, dual-luciferase reporter, RNA pull-down, and RNA binding protein immunoprecipitation assays were applied to verify the interaction between circ_0021350 and its downstream effectors.

Results

Circ_0021350 was significantly elevated in GBM tissues and glioma cells. Overexpression of circ_0021350 promoted glioma cell proliferation and metastatic ability; silencing of circ_0021350 had the opposite effect. Mechanistic analysis revealed that circ_0021350 sponged miR-1207-3p to regulate PIK3R3, whose overexpression reversed the reduction in the malignant biological behavior of glioma cells caused by silencing circ_0021350.

Conclusion

Our findings suggest that circ_0021350 is an oncogenic circRNA in GBM, and the circ_0021350/miR-1207-3p/PIK3R3 axis may serve as a potential therapeutic target in GBM treatment.
Real-world comparison of pembrolizumab and nivolumab in advanced hepatocellular carcinoma
Authors: Chen Yen-Hao , Tsai Ching-Hua , Chen Yen-Yang , Wang Chih-Chi , Wang Jing-Houng , Hung Chao-Hung , Kuo Yuan-Hung
Published: August 2023

Background

Nivolumab and pembrolizumab have not been directly compared in clinical trials, and the aim of this study is to investigate the efficacy and safety of nivolumab versus pembrolizumab in patients with advanced hepatocellular carcinoma (HCC) in real-world practice.

Methods

We retrospectively reviewed patients with HCC who received intravenous nivolumab or pembrolizumab alone as second-line and later therapy. The objective response was determined according to the Response Evaluation Criteria in Solid Tumors criteria version 1.1. Adverse events (AEs) were graded based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. The Kaplan–Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). Prognostic values were estimated using hazard ratios with 95% confidence intervals (CIs).

Results

In total, 120 patients were enrolled, including 95 who received nivolumab and 25 who received pembrolizumab. All patients were staged as Barcelona Clinic Liver Cancer stage C, and 29 patients were classified as Child-Pugh classification B (7). The response rate of the pembrolizumab and nivolumab groups were 8.0% and 7.4%, respectively. There was no significant difference in the median PFS between the pembrolizumab and nivolumab groups (2.7 months versus 2.9 months). The median OS in the nivolumab group was longer than that in the pembrolizumab group (10.8 months versus 8.1 months); however, the difference was not statistically significant. The effects of pembrolizumab and nivolumab on the median PFS and OS were consistent across the subgroups based on baseline characteristics. The severity of all AEs was grades 1–2 without treatment interruption or dose adjustment; there was no statistically significant difference in the incidence of treatment-related AEs between these two groups. Additionally, the percentage of patients receiving subsequent therapy was consistent between the two groups.

Conclusion

The efficacy and safety of pembrolizumab and nivolumab were comparable in the management of patients with pretreated HCC in real-world practice.
Factors influencing fathers’ involvement in the care of hospitalized preterm newborns in Balaka, Malawi
Authors: Mhango Patani , Nyondo-Mipando Alinane Linda
Published: August 2023

Background

Malawi has one of the highest incidences of premature birth, with twice the mortality compared to full-term. Excluding fathers from preterm newborn care has negative consequences, including father feeling powerless, missed bonding opportunities with the newborn, additional strain on the mother, and negative family dynamics such as breakdown in communication, reduced trust, and strained relationships. In Malawi, there is no deliberate policy to have fathers involved in preterm care despite having high incidence of preterm birth and neonatal mortality. There is also limited literature on the factors that influence fathers’ involvement in the care. The aim of the study was to explore factors influencing fathers’ involvement in the care of hospitalized preterm newborns.

Methods

A descriptive qualitative study design was used, guided by Theory of planned behaviour and the model proposed by Lamb on male involvement. Sixteen in-depth interviews were conducted with fathers of preterm infants purposively and conveniently sampled in June 2021. Interviews were digitally recorded and transcribed verbatim. Data were organized and analyzed using Nvivo software and thematic analysis approach was used because the approach allows deeper understanding of the data, identification of patterns and themes, and provides rich insights into participants’ experiences and perspectives.

Results

The barriers and facilitators that influence a father’s involvement in the care of preterm newborn babies include: perceived difficulty with care activities and benefits of involvement, gender roles and socio-cultural beliefs, work and other family responsibilities, social support, baby’s physical appearance/nature and health status, feedback from the baby, multiple births, and hospital’s physical environment and provision of basic needs.

Conclusion

The study found that fathers value their involvement in caring for hospitalized preterm newborns but face barriers. Evidence-based interventions like education programs, training sessions, and support groups can help fathers overcome barriers and promote better outcomes for infants and families.
Genetic contribution of synapse-associated protein 97 to cerebellar functional connectivity changes in first-episode schizophrenia
Authors: Xu Xusan , Luo Shucun , Wang Xiaoxia , Wen Xia , Yin Jingwen , Luo Xudong , He Bin , Liang Chunmei , Xiong Susu , Zhu Dongjian , Lv Dong , Dai Zhun , Lin Juda , Li You , Lin Zhixiong , Chen Wubiao , Luo Zebin , Wang Yajun , Ma Guoda
Published: August 2023

Our previous study data suggested that the synapse-associated protein 97 (SAP97) rs3915512 polymorphism is significantly related to clinical performance in schizophrenia. The cerebellum exhibits abundant expression of SAP97, which is involved with negative symptoms, cognition and emotion in schizophrenia. As functional dysconnectivity with the cortical-subcortical-cerebellar circuitry has been widely shown in patients with schizophrenia, cortical-subcortical-cerebellar dysconnectivity can therefore be considered a possible intermediate phenotype that connects risk genes with schizophrenia. In this study, resting-state functional magnetic resonance imaging (fMRI) was applied to evaluate whether the SAP97 rs3915512 polymorphism changes cortical/subcortical-cerebellar resting-state functional connectivity (RSFC) in 104 Han Chinese subjects (52 first-episode schizophrenia (FES) patients and 52 matched healthy controls (HCs)). To examine RSFC between cortical/subcortical regions and the cerebellum, a ROI (region of interest)-wise functional connectivity analysis was conducted. The association between abnormal cortical/subcortical-cerebellar connectivity and clinical manifestation was further assessed in FES patients with different genotypes. The interactive effect of disease and genotype on RSFC was found between the frontal gyrus (rectus) and cerebellum. A positive correlation was suggested between RSFC in the cerebellum and the hostility scores in FES patients with the A allele, and no correlation was found in FES patients with the TT genotype. The current findings identified that SAP97 may be involved in the process of mental symptoms in FES patients via cerebellar connectivity depending on the rs3915512 polymorphism genotype.
Disruption of brain regional homogeneity and functional connectivity in male NAFLD: evidence from a pilot resting-state fMRI study
Authors: Shu Kun , Ye Xinjian , Song Jiawen , Huang Xiaoyan , Cui Shihan , Zhou Yongjin , Liu Xiaozheng , Han Lu , Yan Zhihan , Liu Kun
Published: August 2023

Background

The neurophysiological mechanisms underlying cognitive deficits in non-alcoholic fatty liver disease (NAFLD) remain unknown. Cognitive changes may be caused by brain alterations in neural activity and functional connectivity (FC).

Aim

This study aims to investigate the alterations between spontaneous brain neural activity and FC in male NAFLD patients and the relationship of neural activity with cognitive performance.

Methods

In this prospective study, 33 male pre-cirrhosis NAFLD subjects and 20 male controls matched for age, education level, and body mass index. All participants underwent resting-state functional magnetic resonance imaging scans and neuropsychological examinations. Regional homogeneity (ReHo) analysis was used to investigate the brain function in NAFLD, and regions with significantly altered ReHo were selected as seeds for subsequent FC analysis. Partial correlation analysis was used to assess the relationships between altered ReHo measures and cognitive performance indicators.

Results

Compared with the controls, the NAFLD patients showed increased ReHo in the opercular part of the right inferior frontal gyrus (IFGoperc) and decreased ReHo in the right middle frontal gyrus (MFG) and left superior parietal gyrus (SPG). The subsequent FC analysis showed increased FC between these regions (right IFGoperc, right MFG, and left SPG) and nodes of the default mode network (DMN) (such as left supraMarginal, left median cingulate and paracingulate gyri, left precuneus, orbital part of left medial frontal gyrus, and bilateral posterior cingulate gyrus). In addition, significant positive correlations were observed between NAFLD patients’ clock drawing test scores and altered ReHo in prefrontal cortices (right IFGoperc and right MFG).

Conclusion

Before developing cirrhosis, NAFLD patients showed altered neural activity in several brain regions and altered FC between the salience network and DMN. These alterations could potentially be a compensatory mechanism to maintain cognitive function in pre-cirrhosis NAFLD patients.