bluuebunny/crossref_metadata_2025 huggingface dataset:
Preferences for attributes of oral antipsychotic treatments: results from a discrete-choice experiment in respondents with schizophrenia or bipolar I disorder
Authors: Doane Michael J. , Boeri Marco , Vass Caroline , Bussberg Cooper , Panchmatia Hemangi R. , Citrome Leslie , Sajatovic Martha
Published: September 2024

Background

Antipsychotic medications are effective treatments for schizophrenia (SZ) and bipolar I disorder (BD-I), but when presented with different treatment options, there are tradeoffs that individuals make between clinical improvement and adverse effects. As new options become available, understanding the attributes of antipsychotic medications that are valued and the tradeoffs that individuals consider when choosing among them is important.

Methods

A discrete-choice experiment (DCE) was administered online to elicit preferences across 5 attributes of oral antipsychotics: treatment efficacy (i.e., improvement in symptom severity), weight gain over 6 months, sexual dysfunction, sedation, and akathisia. Eligible respondents were aged 18–64 years with a self-reported clinician diagnosis of SZ or BD-I.

Results

In total, 144 respondents with SZ and 152 with BD-I completed the DCE. Of those with SZ, 50% identified themselves as female and 69.4% as White, with a mean (SD) age of 41.0 (10.1) years. Of those with BD-I, most identified themselves as female (69.7%) and as White (77.6%), with a mean (SD) age of 40.0 (10.7) years. In both cohorts, respondents preferred oral antipsychotics with better efficacy, less weight gain, no sexual dysfunction or akathisia, and lower risk of sedation. Treatment efficacy was the most important attribute, with a conditional relative importance (CRI) of 31.4% for respondents with SZ and 31.0% for those with BD-I. Weight gain (CRI = 21.3% and 23.1%, respectively) and sexual dysfunction (CRI = 23.4% and 19.2%, respectively) were adverse effects in this study that respondents most wanted to avoid. Respondents with SZ were willing to accept 9.8 lb of weight gain or > 25% risk of sedation for symptom improvement; those with BD-I were willing to accept 8.5 lb of weight gain or a > 25% risk of sedation.

Conclusions

In this DCE, treatment efficacy was the most important attribute of oral antipsychotic medications among respondents with SZ and BD-I. Weight gain and sexual dysfunction were the adverse effects respondents most wanted to avoid; however, both cohorts were willing to accept some weight gain or sedation to obtain better efficacy. These results highlight features that patients value in antipsychotic medications and how they balance benefits and risks when choosing among treatments.
Portable polygraphic device (Somnocheck micro CARDIO®) provides accurate diagnostic information in psychiatric patients at risk for obstructive sleep apnoea: an observational cohort study
Authors: Bailer Maximilian , Stein Eva M. , Sprügel Maximilian I. , Mestermann Stefan , Spitzer Philipp , Utz Janine , Zirlik Sabine , Fuchs Florian S. , Kornhuber Johannes
Published: September 2024

Background

Symptoms of obstructive sleep apnoea (OSA) overlap significantly with those of psychiatric disorders, making accurate diagnosis of OSA challenging within psychiatric settings. Diagnosing OSA in psychiatric patients is crucial because untreated OSA can exacerbate psychiatric symptoms, reduce treatment efficacy, and impair overall quality of life. This study aimed to determine the diagnostic accuracy of a readily accessible procedure for psychiatric patients in a real-world clinical setting by comparing the Somnocheck micro CARDIO® (SCm) portable cardiorespiratory polygraphy device with the gold standard polysomnography (PSG).

Methods

This observational cohort study included consecutive psychiatric patients at intermediate to high risk for OSA based on screening with the STOP-Bang questionnaire, admitted to a single tertiary care centre between June 1, 2016 and December 31, 2022. The Apnoea-Hypopnoea-Index (AHI), Apnoea-Index (AI), Oxygen-Desaturation-Index (ODI), and minimum oxygen saturation were measured sequentially by SCm and PSG.

Results

A total of 57 patients were analysed (median age 62.0 [Interquartile Range (IQR), 51.5–72.5] years; 34 [59.6%] men). Regarding AHI, no significant differences (AHI measured by PSG, median, 16.6 [IQR, 6.2–26.7] vs. AHI measured by SCm, median, 14.9 [IQR, 10.0-22.8]; p = 0.812; r = 0.71) were found between SCm and PSG. AI, ODI and minimum oxygen saturation differed significantly between SCm and PSG. Using optimised cut-off values (any OSA: AHISCm ≥ 9.25), SCm showed high sensitivity (0.894) and high specificity (0.800) for the diagnosis of OSA, with an area under the receiver operating characteristic curve of 0.877.

Conclusions

This study found that the SCm portable device was accurate in identifying psychiatric patients with OSA. AHI measurement by SCm provided reliable diagnostic performance in comparison with the gold standard polysomnography. These findings support the integration of polygraphic measurements into the routine sleep assessment of psychiatric patients. Early and accurate diagnosis of OSA in this population can significantly improve the management of both sleep disorders and psychiatric conditions, potentially enhancing overall treatment outcomes and quality of life for these patients.
Challenges in diagnosis of clinical and subclinical Plasmodium falciparum infections in Ghana and feasibility of reactive interventions to shrink the subclinical reservoir
Authors: Reynders Madeline , Tweneboah Austine , Abbas Dawood Ackom , Opoku Afriyie Stephen , Nketsiah Stephen Nelly , Badu Kingsley , Koepfli Cristian
Published: September 2024

Background

Reactive case detection (RCD) aims to reduce malaria transmission stemming from asymptomatic carriers. Symptomatic individuals diagnosed with malaria at a health centre are followed to their households, where members of the index case and neighbouring households are tested and treated for malaria. An RCD programme was tested in the Ashanti region of Ghana in order to study diagnostic accuracy in the hospital and household settings, assess the prevalence of subclinical infections and possible clustering in index case households, and identify operational challenges for future RCD programmes. Currently, transmission in this region is high, but reactive interventions might become an option once transmission is reduced.

Methods

264 febrile individuals were enrolled at the Mankranso Government Hospital and tested for malaria using rapid diagnostic tests (RDT). From the pool of RDT-positive febrile index cases, 14 successful RCD follow-ups were conducted, and 233 individuals were enrolled from the index case, neighbour, and control households. The sensitivity of diagnostic tools for clinical and subclinical cases was compared, including RDT, expert microscopy by World Health Organization-certified microscopists, field microscopy, and qPCR.

Results

Poor diagnosis and low receptivity to RCD-style follow-ups were major limitations to a successful and effective RCD programme. Field microscopy detected only 49% of clinical infections compared to RDT. 54% of individuals did not agree to a follow-up, and 66% of attempted follow-ups failed. The system effectiveness of RCD, calculated as the product of correctly diagnosed index cases, successful follow-ups, and proportion of asymptomatic infections detected by RDT, was very low at 4.0%.

Conclusions

Due to low system effectiveness and the endemic nature of the disease setting in which asymptomatic prevalence is high and infections are not clustered around index case households, RCD is currently not a feasible option for malaria control in this region. The operational challenges identified through this study may help inform future reactive intervention programme designs once transmission is reduced.
Free fatty acids and mortality among adults in the United States: a report from US National Health and Nutrition Examination Survey (NHANES)
Authors: Li Meng , Zhang Lijing , Huang Bi , Liu Yang , Chen Yang , Lip Gregory Y. H.
Published: September 2024

Background

The relationship between free fatty acids (FFAs) and the risk of mortality remains unclear. There is a scarcity of prospective studies examining the associations between specific FFAs, rather than total concentrations, of their effect on long-term health outcomes.

Objective

To evaluate the correlation between different FFAs and all-cause and cardiovascular mortality in a large, diverse, nationally representative sample of adults in the US, and examine how different FFAs may mediate this association.

Methods

This cohort study included unsaturated fatty acids (USFA) and saturated fatty acids (SFA) groups in the US National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014 and provided blood samples for FFAs levels. Multiple model calibration was performed using Cox regression analysis for known risk factors to explore the associations between FFAs and all-cause and cardiovascular mortality.

Results

In the group of USFA, 3719 people were included, median follow-up, 6.7 years (5.8–7.8 years). In the SFA group, we included 3900 people with a median follow-up, 6.9 years (5.9-8 years). In the USFA group, myristoleic acid (14:1 n-5) (hazard ratio (HR) 1.02 [1.006–1.034]; P = 0.004), palmitoleic acid (16:1 n-7) (HR 1.001 [1.001–1.002]; P < 0.001), cis-vaccenic acid (18:1 n-7) (HR 1.006 [1.003–1.009]; P < 0.001), nervonic acid (24:1 n-9) (HR 1.007 [1.002–1.012]; P = 0.003), eicosatrienoic acid (20:3 n-9) (HR 1.027 [1.009–1.046]; P = 0.003), docosatetraenoic acid (22:4 n-6) (HR 1.024 [1.012–1.036]; P < 0.001), and docosapentaenoic acid (22:5 n-6) (HR 1.019 [1.006–1.032]; P = 0.005) were positively associated with the all-cause mortality, while docosahexaenoic acid (22:6 n-3) had a statistically lower risk of all-cause mortality (HR 0.998 [0.996–0.999]; P = 0.007). Among the SFA group, palmitic acid (16:0) demonstrated a higher risk of all-cause mortality (HR 1.00 [1.00–1.00]; P = 0.022), while tricosanoic acid (23:0) (HR 0.975 [0.959–0.991]; P = 0.002) and lignoceric acid (24:0) (HR 0.992 [0.984–0.999]; P = 0.036) were linked to a lower risk of all-cause mortality. Besides 23:0 and 24:0, the other FFAs mentioned above were linearly associated with the risks of all-cause mortality.

Conclusions

In this nationally representative cohort of US adults, some different FFAs exhibited significant associations with risk of all-cause mortality. Achieving optimal concentrations of specific FFAs may lower this risk of all-cause mortality, but this benefit was not observed in regards to cardiovascular mortality.
DNAm scores for serum GDF15 and NT-proBNP levels associate with a range of traits affecting the body and brain
Authors: Gadd Danni A. , Smith Hannah M. , Mullin Donncha , Chybowska Ola , Hillary Robert F. , Kimenai Dorien M. , Bernabeu Elena , Cheng Yipeng , Fawns-Ritchie Chloe , Campbell Archie , Page Danielle , Taylor Adele , Corley Janie , Del C. Valdés-Hernández Maria , Maniega Susana Muñoz , Bastin Mark E. , Wardlaw Joanna M. , Walker Rosie M. , Evans Kathryn L. , McIntosh Andrew M. , Hayward Caroline , Russ Tom C. , Harris Sarah E. , Welsh Paul , Sattar Naveed , Cox Simon R. , McCartney Daniel L. , Marioni Riccardo E.
Published: September 2024

Background

Plasma growth differentiation factor 15 (GDF15) and N‐terminal proB‐type natriuretic peptide (NT‐proBNP) are cardiovascular biomarkers that associate with a range of diseases. Epigenetic scores (EpiScores) for GDF15 and NT-proBNP may provide new routes for risk stratification.

Results

In the Generation Scotland cohort (N ≥ 16,963), GDF15 levels were associated with incident dementia, ischaemic stroke and type 2 diabetes, whereas NT-proBNP levels were associated with incident ischaemic heart disease, ischaemic stroke and type 2 diabetes (all PFDR < 0.05). Bayesian epigenome-wide association studies (EWAS) identified 12 and 4 DNA methylation (DNAm) CpG sites associated (Posterior Inclusion Probability [PIP] > 95%) with levels of GDF15 and NT-proBNP, respectively. EpiScores for GDF15 and NT-proBNP were trained in a subset of the population. The GDF15 EpiScore replicated protein associations with incident dementia, type 2 diabetes and ischaemic stroke in the Generation Scotland test set (hazard ratios (HR) range 1.36–1.41, PFDR < 0.05). The EpiScore for NT-proBNP replicated the protein association with type 2 diabetes, but failed to replicate an association with ischaemic stroke. EpiScores explained comparable variance in protein levels across both the Generation Scotland test set and the external LBC1936 test cohort (R2 range of 5.7–12.2%). In LBC1936, both EpiScores were associated with indicators of poorer brain health. Neither EpiScore was associated with incident dementia in the LBC1936 population.

Conclusions

EpiScores for serum levels of GDF15 and Nt-proBNP associate with body and brain health traits. These EpiScores are provided as potential tools for disease risk stratification.
HBx promotes tumorigenicity through RRM2-mediated autophagy in hepatocellular carcinoma
Authors: Li Yaqun , Wang Furan , Geng Zikai , He Tianye , Song Yun , Wu Jian , Wang Bin
Published: September 2024

Background

Hepatitis B virus (HBV) infection can exacerbate liver disease progression through multiple mechanisms, eventually leading to hepatocellular carcinoma (HCC). HBV-encoded oncogene X protein (HBx), a key regulatory protein of HBV infection, serves as a positive regulator of hepatocarcinogenesis. The indispensability of the M2 subunit of ribonucleotide-diphosphate reductase (RRM2) lies in its role in facilitating DNA replication and repair processes. In our previous investigation, it was postulated that the gene RRM2 exhibits elevated expression levels in several categories of malignant tumors, particularly in HBV-related HCC. Additionally, it was observed that RRM2 is present within protein complexes that are centered on HBx. In the present investigation, the objective of this work was to investigate the potential relationship between the elevated expression of RRM2 in HBV-related HCC and the influence of HBx on this expression. The study attempted to determine the specific mechanism by which RRM2 is implicated in the promotion of hepatocarcinogenesis by HBx. There have been multiple scholarly proposals suggesting that the induction of autophagy by HBx is a significant intermediary factor in the development of HCC. However, the precise carcinogenic function of HBx-induced autophagy remains a subject of debate.

Results

This work initially investigated the impact of suppressing cellular autophagy on the malignant biological behaviors of HBx-promoted cells using an in vitro cellular model. The findings revealed that the suppression of cellular autophagy partially disrupted the oncogenic effects of HBx. In light of this, we proceeded to conduct more investigations into the regulatory association between RRM2 and HBx-induced autophagy in the upstream-downstream context. Our data indicate that HBx proteins increase the expression of RRM2. Suppression of RRM2 expression not only hinders HBx-induced autophagy, but also worsens the cellular G1/S blockage and reduces the HBx-induced malignant growth of hepatocellular carcinoma tumors, while stimulating apoptosis.

Conclusions

Therefore, we hypothesised that RRM2 is a potential downstream target of HBx-induced hepatocarcinogenesis, and mining the oncogenic mechanism of RRM2 is significant in exploring the preventive treatment of HBV-related HCC.
Dietary supplementation of valine, isoleucine, and tryptophan may overcome the negative effects of excess leucine in diets for weanling pigs containing corn fermented protein
Authors: Mallea Andrea P. , Espinosa Charmaine D. , Lee Su A , Cristobal Minoy A. , Torrez-Mendoza Leidy J. , Stein Hans H.
Published: September 2024

Background

Diets with high inclusion of corn co-products such as corn fermented protein (CFP) may contain excess Leu, which has a negative impact on feed intake and growth performance of pigs due to increased catabolism of Val and Ile and reduced availability of Trp in the brain for serotonin synthesis. However, we hypothesized that the negative effect of using CFP in diets for weanling pigs may be overcome if diets are fortified with crystalline sources of Val, Trp, and (or) Ile.

Methods

Three hundred and twenty weanling pigs were randomly allotted to one of 10 dietary treatments in a completely randomized design, with 4 pigs per pen and 8 replicate pens per treatment. A corn-soybean meal diet and 2 basal diets based on corn and 10% CFP or corn and 20% CFP were formulated. Seven additional diets were formulated by fortifying the basal diet with 20% CFP with Ile, Trp, Val, Ile and Val, Ile and Trp, Trp and Val, or Ile, Trp and Val. A two-phase feeding program was used, with d 1 to 14 being phase 1 and d 15 to 28 being phase 2. Fecal scores were recorded every other day. Blood samples were collected on d 14 and 28 from one pig per pen. On d 14, fecal samples were collected from one pig per pen in 3 of the 10 treatments to determine volatile fatty acids, ammonium concentration, and microbial protein. These pigs were also euthanized and ileal tissue was collected.

Results

There were no effects of dietary treatments on any of the parameters evaluated in phase 1. Inclusion of 10% or 20% CFP in diets reduced (P < 0.05) final body weight on d 28, and average daily gain (ADG) and average daily feed intake (ADFI) in phase 2 and for the entire experimental period. However, pigs fed the CFP diet supplemented with Val, Ile, and Trp had final body weight, ADFI, ADG and gain to feed ratio in phase 2 and for the entire experiment that was not different from pigs fed the control diet. Fecal scores in phase 2 were reduced (P < 0.05) if CFP was used.

Conclusions

Corn fermented protein may be included by up to 20% in diets for weanling pigs without affecting growth performance, gut health, or hindgut fermentation, if diets are fortified with extra Val, Trp, and Ile. Inclusion of CFP also improved fecal consistency of pigs.
The abundance of snail hosts mediates the effects of antagonist interactions between trematodes on the transmission of human schistosomes
Authors: Douchet Philippe , Haegeman Bart , Allienne Jean-François , Boissier Jérôme , Senghor Bruno , Rey Olivier
Published: September 2024

Background

Combating infectious diseases and halting biodiversity loss are intertwined challenges crucial to ensure global health. Biodiversity can constrain the spread of vector-borne pathogens circulation, necessitating a deeper understanding of ecological mechanisms underlying this pattern. Our study evaluates the relative importance of biodiversity and the abundance of Bulinus truncatus, a major intermediate host for the trematode Schistosoma haematobium on the circulation of this human pathogen at aquatic transmission sites.

Methods

We combined mathematical modelling and a molecular based empirical study to specifically assess the effect of co-infections between S. haematobium and other trematodes within their B. truncatus snail hosts; and B. truncatus abundance at transmission sites, on the production of S. haematobium infective cercariae stages released into the aquatic environment.

Results

Our modelling approach shows that more competitive trematode species exploiting B. truncatus as an intermediate host at the transmission site level leads to higher co-infection rates within snail hosts, subsequently reducing the production of S. haematobium cercariae. Conversely, an increase in B. truncatus abundance results in lower co-infection rates, and a higher proportion of S. haematobium cercariae released into the environment. Our empirical data from the field support these findings, indicating a significant negative effect of local trematode species richness (P-value = 0.029; AIC = 14.9) and co-infection rates (P-value = 0.02, AIC = 17.4) on the dominance of S. haematobium based on our GLMM models, while B. truncatus abundance positively influences S. haematobium dominance (P-value = 0.047, AIC = 20.1).

Conclusions

Our study highlights the importance of biodiversity in influencing the transmission of S. haematobium through the effect of antagonistic interactions between trematodes within bulinid snail hosts. This effect intensifies when B. truncatus populations are low, promoting co-infections within snails. In line with the One Health concept, our results suggest that maintaining high level of freshwater biodiversity to sustain global trematode diversity at transmission sites can help reducing the circulation of Schistosoma species locally.

Graphical Abstract
Reliability and validity of the German version of the University of Jyvaskyla Active Aging Scale (UJACAS-G)
Authors: Hinrichs Timo , Rantanen Taina , Portegijs Erja , Nebiker Lukas , Rössler Roland , Schwendinger Fabian , Schmidt-Trucksäss Arno , Roth Ralf
Published: September 2024

Background

The University of Jyvaskyla Active Aging Scale (UJACAS) assesses active aging through willingness, ability, opportunity, and frequency of involvement in activities. Recognizing the lack of a German version, the Finnish original was translated (UJACAS-G). This study aimed: (1) to evaluate the test-retest reliability of UJACAS-G; and (2) to explore correlations with health-related parameters (concurrent validity).

Methods

The study (test-retest design) targeted healthy older adults aged 65+. Reliability of UJACAS-G (total and subscores) was assessed using Bland-Altman analyses and Intraclass Correlation Coefficients (ICCs). Furthermore, correlations (Spearman’s rho) between UJACAS-G scores and physical function (walking speed, handgrip strength, balance, 6-minute walk distance), physical activity (International Physical Activity Questionnaire), life-space mobility (Life-Space Assessment), and health-related quality of life (Short Form-36 Health Survey) were calculated.

Results

Bland-Altman analyses (N = 60; mean age 72.3, SD 5.9 years; 50% women) revealed mean differences close to zero and narrow limits of agreement for all scores (total score: mean difference −1.9; limits −31.7 to 27.9). The ability subscore showed clustering at its upper limit. ICC was 0.829 (95% CI 0.730 to 0.894) for the total score and ranged between 0.530 and 0.876 for subscores (all p-values < 0.001). The total score correlated with walking speed (rho = 0.345; p = 0.008), physical activity (rho = 0.279; p = 0.033) and mental health (rho = 0.329; p = 0.010).

Conclusions

UJACAS-G is reliable for assessing active aging among German-speaking healthy older adults. A potential ‘ceiling effect’ regarding the ability subscore should be considered when applying UJACAS-G to well-functioning populations. Analyses of concurrent validity indicated only weak correlations with health-related parameters.
Indirect bypass surgery as a line of management of pediatric moyamoya disease
Authors: Farouk Mohamed , El-Tantawy Ibrahim Mohamed , Kassem Mohamed Ali , Ezzeldein Ashraf , Nabeeh Mostafa Mahmoud , Elsherbini Mohamed M.
Published: September 2024

Moyamoya disease (MMD) is a chronic, rare cerebrovascular disorder of unknown cause featured by extensive narrowing of the terminal internal carotid artery (ICA) and its main branches. As a compensatory mechanism, perforators dilate forming fragile collateral vessels that appear as an abnormal vascular network resembling ‘puff of smoke drifting in the air’ observed via angiography around stenotic area in the brain.

Patients and methods

The database of the current hospital was retrospectively studied. All patients with ischemic strokes owing to MMD treated with surgical revascularization between January 2015 and December 2022 were included. MMD was identified on catheter-based digital subtraction angiography (DSA) by the presence of stenosis at the terminal portions of both internal carotid arteries and the development of abnormal collateral “moyamoya vessels” around the base of the brain. Clinical, radiological and follow-up data were retrospectively analyzed.

Results

During the mentioned time window, nine patients were diagnosed with moyamoya disease among all pediatric patients with established diagnosis of ischemic stroke in our institute; six of them underwent surgery. Unilateral EDMS was performed in 5 cases (83.3%), while one patient (16.67%) underwent staged bilateral surgeries with no added neurological deficit.

Conclusion

Indirect revascularization surgery for pediatric moyamoya-related stroke patients has high rates of reperfusion and promising outcomes.
Investigating the effects of percutaneous endovascular aneurysm repair for abdominal aortic aneurysm on the lumen size of the common femoral artery
Authors: Ong Wilson Wei Xiang , Tay Hsien Ts’ung , Chong Tze Tec
Published: September 2024

Background

Percutaneous endovascular aneurysm repair (PEVAR) is the definitive therapy of choice for abdominal aortic aneurysms worldwide. However, current literature regarding the anatomic changes in the common femoral artery (CFA) post-PEVAR is sparse and contradictory, and a significant proportion of these studies did not control for the potential confounding effects of ethnicity. Thus, this study aims to investigate the anatomical effects of PEVAR on the CFA using an Asian study cohort.

Methods

Between January 2019 and September 2023, the records of 113 patients who received PEVAR were reviewed. Groins with previous surgical interventions were excluded. The most proximate pre- and postoperative CT angiography of patients receiving PEVAR via the Perclose ProGlide™ Suture-Mediated Closure System were retrospectively analysed for changes in both the CFA inner luminal diameter (ID) and outer diameter (OD), the latter also encompassing the arterial walls. Access site complications within 3 months post-PEVAR were also recorded per patient.

Results

One hundred seventeen groins from 60 patients were included in this study, with 1 report of pseudoaneurysm. The CFA ID exhibited a 0.167 mm decrease (p-value = 0.0403), while the OD decreased by 0.247 mm (p-value = 0.0107). This trend persisted when the data was separately analysed with the common cardiovascular risk factors of diabetes mellitus, hypertension and hyperlipidaemia.

Conclusion

Our analysis demonstrated a statistically significant decrease in the CFA diameters post-PEVAR. However, the percentage changes were below established flow-limiting values, as reflected by the single access site complication reported. Hence, our findings give confidence in the safety profile of this procedure, even with the reported smaller baseline CFA lumen size in Asians. Moving forward, similar longer-term studies should be considered to characterise any late postoperative effects.

Graphical Abstract
Gut microbiome influences efficacy of Endostatin combined with PD-1 blockade against colorectal cancer
Authors: Xu Jie , Tian Yaomei , Zhao Binyan , Hu Die , Wu Siwen , ma Jing , Yang Li
Published: September 2024

The combination of anti-angiogenic drugs and immune checkpoint inhibitors (ICIs) in the treatment of tumors is emerging as a way to improve ICIs-resistant tumor therapy. In addition, gut microbes (GMs) are involved in angiogenesis in the tumor microenvironment and are also associated with the antitumor function of immune checkpoint inhibitors. However, it is unclear whether gut microbes have a role in anti-tumor function in the combination of anti-angiogenic drugs and immune checkpoint inhibitors for cancer treatment. Endostatin, an angiogenesis inhibitor, has been widely used as an antiangiogenic therapy for cancer. We showed that combined therapy with an adenovirus encoding human endostatin, named Ad-E, and PD-1 blockade dramatically abrogated MC38 tumor growth. The structure of intestinal microbes in mice was changed after combination treatment. We found that the antitumor function of combination therapy was inhibited after the elimination of intestinal microbes. In mice with depleted microbiota, oral gavage of Bacteroides fragilis salvaged the antitumor effects of combination Ad-E and αPD-1 monoclonal antibody (mAb) to a certain extent. Further, Bacteroides fragilis could improve CD3+T cells, NK cells, and IFNγ+CD8+ T cells in the tumor microenvironment to inhibit tumor growth. Besides, Bacteroides fragilis might restore antitumor function by down-regulating isobutyric acid (IBA). Our results suggested that GMs may be involved in the combination of Ad-E and αPD-1 mAb for cancer treatment, which has oncological implications for tumor growth dynamics and cancer immune surveillance.
Parametric study of free turbulent slurry jet: influence of particle size and particle concentration on the flow dynamics and thermal behavior of high-speed slurry jet
Authors: Sharma Nilesh Kumar , Dewangan Satish Kumar , Gupta Pankaj Kumar
Published: September 2024

A detailed computational investigation was conducted to explore the dynamics of high-speed free slurry jets, with a focus on how variations in abrasive size and concentration affect their behavior. The study yielded several significant observations: Firstly, it was observed that slurry jets containing larger particles exhibited notably higher average velocities, attributed to their inherent self-similar characteristics. Specifically, at the far field of the jet, slurry jets with larger particle sizes demonstrated a 15% increase in velocity compared to those with smaller particles. Additionally, an analysis of turbulent intensity revealed that beyond a certain axial distance (x/D = 10), turbulence levels progressively increased. However, intriguingly, for slurry jets with a high concentration (Co = 15%), there was a notable decrease (28%) in turbulent intensity compared to water jets, indicating a complex interplay between particle size and concentration. Secondly, the study found that as the concentration of particles in the slurry jet increased, there was a corresponding rise in the bulk temperature of the jet. This phenomenon was primarily attributed to the heightened thermal conductivity resulting from the increased density of particles in the water. Furthermore, an examination of the Nusselt number revealed interesting trends. While the Nusselt number exhibited a peak near the nozzle exit, indicative of enhanced heat transfer in this region, it showed a decremental trend along the axial direction of the jet, attributable to jet divergence. In summary, the computational analysis provided valuable insights into the behavior of high-speed slurry jets, highlighting the intricate relationships between abrasive size, concentration, velocity distribution, and thermal characteristics. These findings contribute to a deeper understanding of slurry jet dynamics and have significant implications for various industrial applications.
Whole Lung Irradiation in Rhabdomyosarcoma With Lung Metastases: A Report From the Soft Tissue Sarcoma Committee of the Children's Oncology Group
Authors: Luo Leo Y. , Xue Wei , Qumseya Amira , Vasquez Juan C. , Venkatramani Rajkumar , Wolden Suzanne L. , Casey Dana L.
Published: September 2024

PURPOSE

Patients with rhabdomyosarcoma with metastatic disease have a poor prognosis despite therapy intensification. The aim of this study was to investigate the efficacy of whole lung irradiation (WLI) in patients with rhabdomyosarcoma and lung metastases.

METHODS

Patients with rhabdomyosarcoma with lung metastases enrolled on four Children's Oncology Group protocols (D9802, D9803, ARST08P1, ARST0431) were retrospectively reviewed. Event-free survival (EFS) and overall survival (OS) were compared between patients who received and did not receive WLI.

RESULTS

In 143 patients with rhabdomyosarcoma with lung metastases, 65 patients (45.5%) received WLI and 78 patients (54.5%) did not receive WLI despite protocol requirements. The 5-year EFS was 38.3% (95% CI, 24.8 to 51.8) in patients who received WLI and 25.2% (95% CI, 13.8 to 36.6) in patients who did not receive WLI (
P
= .0496). The 5-year OS was 45.5% (95% CI, 31.8 to 59.3) in patients who received WLI and 32.4% (95% CI, 20.4 to 44.4) in patients who did not receive WLI (
P
= .08). In exploratory subgroup analyses, the benefit of WLI on EFS and OS was significant in patients 10 years and older. Other clinical factors associated with EFS on univariable analysis included age, histology FOXO1 fusion status, number of metastatic sites, location of metastatic sites, and Oberlin Score.

CONCLUSION

WLI is associated with improved EFS in patients with rhabdomyosarcoma with lung metastases. These results highlight the potential importance of WLI and need for more stringent protocol compliance for administering WLI.
Metabolic Crosstalk in Multimorbidity: Identifying Compensatory Effects Among Diabetes, Hypertension, and Dyslipidemia
Authors: Pitti Erica , Vanni Domitilla , Viceconte Nicola , Lembo Angelo , Tanzilli Gaetano , Raparelli Valeria , Petrella Greta , Cicero Daniel O
Published: September 2024

Context

Metabolomics is becoming increasingly popular for detecting markers that indicate the presence of a specific disease. However, it is usually applied to studying individual ailments, yielding results that may not be directly relevant to people with multiple health conditions.

Objective

Our study proposes a different approach to explore metabolic crosstalk between various disease states.

Design, Setting, and Patients

We conducted a study on subjects at medium to high risk of developing coronary artery disease. We measured the plasma levels of 83 metabolites using nuclear magnetic resonance and analyzed the connections between these metabolites and various risk factors such as diabetes, hypertension, and dyslipidemia. Linear regression and multivariate analysis were combined for this purpose.

Results

Inspection of the metabolic maps created by our analysis helped us efficiently compare profiles. In this way, it was possible to discover opposing metabolic features among single conditions and their combination. Furthermore, we found compensating metabolic effects between diabetes, hypertension, and dyslipidemia involving mainly ketone body metabolism and fatty acid β-oxidation.

Conclusion

Our study introduces a novel approach to investigating how metabolism reacts to the simultaneous presence of multiple health conditions. This has allowed the detection of potential compensatory effects between diabetes, hypertension, and dyslipidemia, highlighting the complexity of metabolic crosstalk in patients with comorbidities. A better understanding of metabolic crosstalk like this could aid in developing focused treatments, resulting in improved therapeutic results.
Pro-Con Debate: Anesthesiologists Should Be Responsible for Treating Preoperative Anemia
Authors: Hensley Nadia B. , Frank Steven M. , Nemergut Edward C. , Neely Grant A.
Published: September 2024

In this Pro-Con commentary article, we discuss whether anesthesiologists should be responsible for treating preoperative anemia. This debate was proposed based on the article published in this issue of Anesthesia & Analgesia by Warner et al, which is an advisory on managing preoperative anemia endorsed by both the Society of Cardiovascular Anesthesiologists and the Society for Advancement of Patient Blood Management. All evidence suggests that anemia is not just an innocent “bystander” which can be solved by transfusion. In fact, both anemia and transfusion are independently associated with adverse outcomes, so why not avoid both? It just makes sense that patients show up for surgery with enough red blood cells to avoid needing transfusion with someone else’s. Even if we agree that preoperative anemia is worth treating before surgery, the question remains who should be responsible for doing so, and therein lies the reason for this Pro-Con debate. Should it be the responsibility of the anesthesiologist, or not? Let the readers decide.
Eternal Sovereigns
Authors: Bell Gloria Jane
Published: September 2024

In 1925, Pius XI staged the Vatican Missionary Exposition in Rome's Vatican City. Offering a narrative of the Catholic Church's beneficence to a global congregation, the exposition displayed thousands of cultural belongings stolen from Indigenous communities across Turtle Island, which were seen by one million pilgrims. Gloria Bell's Eternal Sovereigns offers critical revision to that story. Bell reveals the tenacity, mobility, and reception of Indigenous artists, travelers, and activists in 1920s Rome. Animating these conjunctures, the book foregrounds competing claims to sovereignty from Indigenous and papal perspectives. Bell deftly juxtaposes the “Indian Museum” of nineteenth-century sculptor Ferdinand Pettrich with the oeuvre of Indigenous artist Edmonia Lewis. Bell analyzes Indigenous cultural belongings made by artists from diverse nations including Cree, Lakota, Anishinaabe, Nipissing, Kanien'kehá:ka, Wolastoqiyik, and Kwakwaka'wakw. Drawing on years of archival research and field interviews, Bell provides insight into the Catholic Church's colonial collecting and its ongoing ethnological display practices. Written in a voice that questions the academy's staid conventions, the book reclaims Indigenous belongings and other stolen treasures that remain imprisoned in the stronghold of the Vatican Museums.
Elevating microRNA levels by targeting biogenesis with steric-blocking antisense oligonucleotides
Authors: Havens Mallory A. , Hinrich Anthony J. , Rigo Frank , Hastings Michelle L.
Published: September 2024

MicroRNAs (miRNAs) are regulators of gene expression, and their dysregulation is linked to cancer and other diseases, making them important therapeutic targets. Several strategies for targeting and modulating miRNA activity are being explored. For example, steric-blocking antisense oligonucleotides (ASOs) can reduce miRNA activity by either blocking binding sites on specific mRNAs or base-pairing to the miRNA itself to prevent its interaction with the target mRNAs. ASOs have been less explored as a tool to elevate miRNA levels, which could also be beneficial for treating disease. In this study, using thePKD1/miR-1225 gene locus as an example, where miR-1225 is located within aPKD1intron, we demonstrate an ASO-based strategy that increases miRNA abundance by enhancing biogenesis from the primary miRNA transcript. Disruptions inPKD1and miR-1225 are associated with autosomal dominant polycystic kidney disease (ADPKD) and various cancers, respectively, making them important therapeutic targets. We investigatedPKD1sequence variants reported in ADPKD that are located within the sequence shared by miR-1225 andPKD1,and identified one that causes a reduction in miR-1225 without affectingPKD1. We show that this reduction in miR-1225 can be recovered by treatment with a steric-blocking ASO. The ASO-induced increase in miR-1225 correlates with a decrease in the abundance of predicted miR-1225 cellular mRNA targets. This study demonstrates that miRNA abundance can be elevated using ASOs targeted to the primary transcript. This steric-blocking ASO-based approach has broad potential application as a therapeutic strategy for diseases that could be treated by modulating miRNA biogenesis.
Iron overload and liver function in patients with beta thalassemia major: A cross sectional study
Authors: Faruqi Amna , Zafar Tooba , Subuctageen Sikander , Mughal Irfan Afzal
Published: September 2024

Objective: In thalassemia major, repeated blood transfusions result in iron overload causing organ damage. The objective of this study was assessment of liver enzymes in patients with Thalassemia major and to observe their association with ferritin.
Method: A cross-sectional study was performed, at Islamabad Medical and Dental College and its affiliated Akbar Niazi Teaching Hospital from November 2021 till August 2022. Serum ferritin, AST, ALT, and total bilirubin levels were determined, in 135 patients of beta thalassemia major receiving transfusions. Data analysis was performed using SPSS Version 20. For categorical variables, calculation of frequencies and percentages was performed. Mean (± standard deviation) was determined for quantitative variables. ANOVA with post hoc Tukey’s test was used for determining association between liver enzymes and serum ferritin. A p-value of <0.05 was considered significant. The correlation between ferritin and LFTs was determined by Pearson’s correlation coefficient.
Results: Patients had an age range of 7-30 years, and males constituted 51% of sample. Mean level of ferritin was 6062.61 + 3641.79 ng/ml, with an insignificant difference between the genders (p =0.366). The levels of AST, ALT and bilirubin were perceived to show a significant increase in patients with ferritin levels >5000ng/ml, when compared with patients having ferritin levels < 2,500 ng/ml. A significant positive correlation of increasing serum ferritin levels was observed with ALT (r= 0.682), to a lesser extent with AST (r = 0.532), and only a weak correlation with serum bilirubin (r = 0.350).
Conclusion: Liver damage was caused by increased iron deposition. LFTs should be performed regularly to detect and reduce liver damage by increasing chelation therapy, thereby reducing morbidity and mortality due to thalassemia.
doi: https://doi.org/10.12669/pjms.40.9.8961
How to cite this: Faruqi A, Zafar T, Subuctageen S, Mughal IA. Iron overload and liver function in patients with beta thalassemia major: A cross sectional study. Pak J Med Sci. 2024;40(9):---------. doi: https://doi.org/10.12669/pjms.40.9.8961
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Assessing the cytotoxicity of phenolic and terpene fractions extracted from Iraqi Prunus arabica against AMJ13 and SK-GT-4 human cancer cell lines
Authors: Mahmood Matin Adil , Abd Abdulkareem Hameed , Kadhim Enas Jawad
Published: September 2024

Background: Breast and esophageal cancer are the most aggressive and prominent causes of death worldwide. In addition, these cancers showed resistance to current chemotherapy regimens with limited success rates and fatal outcomes. Recently many studies reported the significant cytotoxic effects of phenolic and terpene fractions extracted from various Prunus species against different cancer cell lines. As a result, it has a good chance to be tested as a complement or replacement for standard chemotherapies. Methods: The study aimed to evaluate the cytotoxicity of phenolic and terpene fractions extracted from Iraqi Prunus arabica on breast (AMJ13) and esophageal (SK-GT-4) cancer cell lines by using the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide). Analysis using the Chou-Talalay method was performed to assess the synergistic effect between the extracted fractions and chemotherapeutic agent (docetaxel). Moreover, high-performance liquid chromatography (HPLC) analysis was conducted for the quantitative determination of different bioactive molecules of both phenolic and terpene fractions in the extract. Results: According to the findings, the treatment modalities significantly decreased cancer cell viability of AMJ13 and SK-GT-4 and had insignificant cytotoxicity on the normal cells (normal human fibroblast cell line) (all less than 50% cytotoxicity). Analysis with Chou-Talalay showed a strong synergism with docetaxel on both cancer cell lines (higher cytotoxicity even in low concentrations) and failed to induce cytotoxicity on the normal cells. Important flavonoid glycosides and terpenoids were detected by HPLC, in particularly, ferulic acid, catechin, chlorogenic acid, β-sitosterol, and campesterol. Conclusions: In conclusion, the extracted fractions selectively inhibited the proliferation of both cancer cell lines and showed minimal cytotoxicity on normal cells. These fractions could be naturally derived drugs for treating breast and esophageal cancers.
Effects of thermomechanical parameters on surface texture in filament materials extrusion: outlook and trends
Authors: Kechagias John D.
Published: September 2024

The material extrusion process has been widely used to manufacture custom products. However, the surface texture varies due to the additive mechanism of the process, which depends on the layer height and surface orientation, resulting in varying average surface roughness values for inclined, flat and vertical surfaces. Different strand welding conditions result in non-uniform internal stresses, surface distortions, layer traces, weak bonding, non-uniform pores and material overflow. This paper comprehensively examines material extrusion process achievements in surface texture quality and studies and summarises the most influential processing parameters. Parameter effects are critically discussed for each topic; flat, inclined, and vertical surfaces. The results of this research help reduce post-processing.
Characteristics of primary tuberculous mastitis in tuberculosis endemic country: A case series
Authors: Maulanisa Sinta Chaira , Fidiawati Wiwit Ade , Mardhiyah Farah
Published: September 2024

Tuberculous mastitis (TM) is a rare form of tuberculosis, occurring as a primary disease when there is no evidence of tuberculosis in other locations. There are no clear clinical features of TM, especially in the absence of a previous tuberculosis infection. Due to its unclear clinical picture, diagnosis is difficult, and it is often confused with breast carcinoma or pyogenic abscesses. The aim of this study was to report our experience and discuss the characteristics and diagnostic modalities in cases of primary TM in a tuberculosis-endemic area. Method A case series study was conducted at the Arifin Achmad Regional Hospital, reporting four cases of primary tuberculous mastitis in January 2024. The patients were women aged 24-41 years. Case presentation All patients presented with complaints of breast pain for the last 2 weeks to 2 months and complained of symptoms in the form of a lump in the breast that was reddish in colour and mastalgia. One patient was diagnosed during pregnancy, and one had a history of prior breastfeeding. One patient presented with FNAB results for breast carcinoma. The other patient complained of an ulcer on her breast. Physical examination revealed axillary lymphadenopathy in all patients. Histopathological examination revealed tuberculous mastitis in all patients and 1 with tuberculous mastitis, fibrocystic changes, and Atypical Ductal Hyperplasia (ADH). Conclusion Patients with tuberculous mastitis who visited our institution had symptoms similar to those of abscesses and breast cancer. The FNAC test is the most reliable, but false-negative results can occur. Diagnosis requires teamwork between the patient’s doctor, anatomical pathologist, and radiologist. This research requires a larger scale to describe actual conditions.