bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and efficacy analysis of neoadjuvant pertuzumab, trastuzumab and standard chemotherapy for HER2–positive early breast cancer: real–world data from NeoPowER study
Authors: Canino Fabio , Barbolini Monica , De Giorgi Ugo , Fontana Tommaso , Gaspari Valeria , Gianni Caterina , Gianni Lorenzo , Maestri Antonio , Minichillo Santino , Moscetti Luca , Mura Antonella , Nicoletti Stefania Vittoria Luisa , Omarini Claudia , Pagani Rachele , Sarti Samanta , Toss Angela , Zamagni Claudio , Cuoghi Costantini Riccardo , Caggia Federica , Antonelli Giuseppina , Baglio Federica , Belluzzi Lorenzo , Martinelli Giulio , Natalizio Salvatore , Ponzoni Ornella , Dominici Massimo , Piacentini Federico
Published: June 2024

Background

The addition of pertuzumab (P) to trastuzumab (H) and standard chemotherapy (CT) as neoadjuvant treatment (NaT) for patients with HER2 + breast cancer (BC), has shown to increase the pathological complete response (pCR) rate, without main safety concerns. The aim of NeoPowER trial is to evaluate safety and efficacy of P + H + CT in a real–world population.

Methods

We retrospectively reviewed the medical records of stage II–III, HER2 + BC patients treated with NaT: who received P + H + CT (neopower group) in 5 Emilia Romagna institutions were compared with an historical group who received H + CT (control group). The primary endpoint was the safety, secondary endpoints were pCR rate, DRFS and OS and their correlation to NaT and other potential variables.

Results

260 patients were included, 48% received P + H + CT, of whom 44% was given anthraciclynes as part of CT, compared to 83% in the control group. The toxicity profile was similar, excluding diarrhea more frequent in the neopower group (20% vs. 9%). Three patients experienced significant reductions in left ventricular ejection fraction (LVEF), all receiving anthracyclines. The pCR rate was 46% (P + H + CT) and 40% (H + CT) (p = 0.39). The addition of P had statistically correlation with pCR only in the patients receiving anthra-free regimens (OR = 3.05,p = 0.047). Preoperative use of anthracyclines (OR = 1.81,p = 0.03) and duration of NaT (OR = 1.18,p = 0.02) were statistically related to pCR. 12/21 distant-relapse events and 14/17 deaths occurred in the control group. Patients who achieve pCR had a significant increase in DRFS (HR = 0.23,p = 0.009).

Conclusions

Adding neoadjuvant P to H and CT is safe. With the exception of diarrhea, rate of adverse events of grade > 2 did not differ between the two groups. P did not increase the cardiotoxicity when added to H + CT, nevertheless in our population all cardiac events occurred in patients who received anthracycline-containing regimens. Not statistically significant, higher pCR rate is achievable in patients receiving neoadjuvant P + H + CT. The study did not show a statistically significant correlation between the addition of P and long-term outcomes.
Carcinoma in situ within the bladder trigone with an isolated metastasis to the prostate without involvement of prostatic urethra: a unique case report
Authors: Batha Omran , Aldolly Ahmed , Alsaffaf Yousef , Hamsho Suaad , Atia Mohammad , Salmeh Fayez , Alia Louei
Published: June 2024

Background

Carcinoma in situ of the bladder is a high-grade cancer that originates in the superficial layer of the bladder. It has the potential to invade nearby organs, and it can spread through blood and lymphatic circulation to distant parts of the body.

Case presentation

A 58-year-old non-smoker male presented with gross and microscopic hematuria. His family history included his father’s recent bladder cancer. Initial investigations showed hematuria, inflammation, negative urine culture, digital rectal examination revealed an enlarged right lobe of the prostate, and an elevated Prostate-Specific Antigen level. Histopathological examination of samples taken from the bladder mucosa and the prostate confirmed urothelial carcinoma in situ in the bladder and prostate. Further evaluation revealed no other metastasis. The tumor was classified as T4aN0M0. The patient underwent radical cystoprostatectomy and histopathological examination showed that the tumor invading the muscularis propria of the bladder as well as the prostatic glands, but no malignancy was found in prostatic urethra and other areas. The patient was discharged three weeks post-operation and completed on adjuvant chemotherapy consisting of Gemcitabine, and Cisplatin to prevent of relapse. The patient is currently in a good healthy.

Conclusion

The occurrence of bladder cancer metastasizing to the prostate without involving the prostatic urethra is uncommon and requires precise diagnostic techniques for accurate tumor classification. Early management is advised to enhance the prognosis for the patient.
A comparative study of microbial changes in dental plaque before and after single- and multiappointment treatments in patients with severe early childhood caries
Authors: Ma Shi Ying , Zhou Qing Nan , Cai Shuang , Zhou Yan , Zhang Xiao Yu , Feng Xiao Yu , Diao Shu , Xi Jin Qiu , Yu Guo Xia , Shang Jia Jian , Yang Ning Yan
Published: June 2024

Background

The status of dental caries is closely related to changes in the oral microbiome. In this study, we compared the diversity and structure of the dental plaque microbiome in children with severe early childhood caries (S-ECC) before and after general anaesthesia and outpatient treatment.

Methods

Forty children aged 3 to 5 years with S-ECC who had completed whole-mouth dental treatment under general anaesthesia (C1) or in outpatient settings (C2) were selected, 20 in each group. The basic information and oral health status of the children were recorded, and the microbial community structure and diversity of dental plaque before treatment (C1, C2), the day after treatment(C2_0D), 7 days after treatment (C1_7D, C2_7D), 1 month after treatment (C1_1M, C2_1M), and 3 months after treatment (C1_3M, C2_3M) were analysed via 16 S rRNA high-throughput sequencing technology.

Results

(1) The alpha diversity test showed that the flora richness in the multiappointment group was significantly greater at posttreatment than at pretreatment (P < 0.05), and the remaining alpha diversity index did not significantly differ between the 2 groups (P > 0.05). The beta diversity analysis revealed that the flora structures of the C1_7D group and the C2_3M group were significantly different from those of the other time points within the respective groups (P < 0.05). (2) The core flora existed in both the pre- and posttreatment groups, and the proportion of their flora abundance could be altered depending on the caries status of the children in both groups. Leptotrichia abundance was significantly (P < 0.05) lower at 7 days posttreatment in both the single- and multiappointment groups. Corynebacterium and Corynebacterium_matruchotii were significantly more abundant in the C1_1M and C1_3M groups than in the C1 and C1_7D groups (P < 0.05). Streptococcus, Haemophilus and Haemophilus_parainfluenzae were significantly more abundant in the C1_7D group than in the other groups (P < 0.05).

Conclusion

A single session of treatment under general anaesthesia can cause dramatic changes in the microbial community structure and composition within 7 days after treatment, whereas treatment over multiple appointments may cause slow changes in oral flora diversity.
Health care providers’ perspectives on the need for palliative care in Upper Egypt: a descriptive exploratory study including children and adult patients
Authors: Osman Atiat , Horvick Savannah Gail , Dias Nancy
Published: June 2024

Background

Only four centers in Egypt provide Palliative Care (PC) for adult cancer patients and one provides care for pediatric cancer patients. While PC is not widely utilized in Egypt, this study aims to assess patients’ need for PC from the providers’ perspective. The primary objectives were to assess providers’ knowledge about PC, understand patients’ needs, and compare children’s and adults’ needs for PC.

Methods

A descriptive exploratory design was utilized. Patients were recruited from a cancer center in Qena Governorate, Egypt. All 108 nurses and physicians in the cancer center were interviewed to assess their perspectives about PC and patients’ need for it.

Results

Of the 108 care providers, more than 60% of the providers were not familiar with the concept of PC and did not participate in related activities, and more than 77% did not receive any training on the topic. All the providers reported there is no specific policy for end-of-life care. More than 60% of the providers responded that their patients do not need PC as the providers believe that PC provided only for end-stage patients. 50% of the providers see that PC has benefits such as pain relief and symptom management. No major differences were noted between pediatric and adult PC needs.

Conclusion

The results of this study provide foundational evidence of providers’ lack of experience with and understanding of palliative care. This deficit is creating a barrier to providing palliative care in Egypt.
Bi-directionalized promoter systems allow methanol-free production of hard-to-express peroxygenases with Komagataella Phaffii
Authors: Besleaga Mihail , Zimmermann Christian , Ebner Katharina , Mach Robert L. , Mach-Aigner Astrid R. , Geier Martina , Glieder Anton , Spadiut Oliver , Kopp Julian
Published: June 2024

Background

Heme-incorporating peroxygenases are responsible for electron transport in a multitude of organisms. Yet their application in biocatalysis is hindered due to their challenging recombinant production. Previous studies suggest Komagataella phaffi to be a suitable production host for heme-containing enzymes. In addition, co-expression of helper proteins has been shown to aid protein folding in yeast. In order to facilitate recombinant protein expression for an unspecific peroxygenase (AnoUPO), we aimed to apply a bi-directionalized expression strategy with Komagataella phaffii.

Results

In initial screenings, co-expression of protein disulfide isomerase was found to aid the correct folding of the expressed unspecific peroxygenase in K. phaffi. A multitude of different bi-directionalized promoter combinations was screened. The clone with the most promising promoter combination was scaled up to bioreactor cultivations and compared to a mono-directional construct (expressing only the peroxygenase). The strains were screened for the target enzyme productivity in a dynamic matter, investigating both derepression and mixed feeding (methanol-glycerol) for induction. Set-points from bioreactor screenings, resulting in the highest peroxygenase productivity, for derepressed and methanol-based induction were chosen to conduct dedicated peroxygenase production runs and were analyzed with RT-qPCR. Results demonstrated that methanol-free cultivation is superior over mixed feeding in regard to cell-specific enzyme productivity. RT-qPCR analysis confirmed that mixed feeding resulted in high stress for the host cells, impeding high productivity. Moreover, the bi-directionalized construct resulted in a much higher specific enzymatic activity over the mono-directional expression system.

Conclusions

In this study, we demonstrate a methanol-free bioreactor production strategy for an unspecific peroxygenase, yet not shown in literature. Hence, bi-directionalized assisted protein expression in K. phaffii, cultivated under derepressed conditions, is indicated to be an effective production strategy for heme-containing oxidoreductases. This very production strategy might be opening up further opportunities for biocatalysis.
An urgent need for community lot testing of lateral flow fentanyl test strips marketed for harm reduction in Northern America
Authors: Lieberman Marya , Badea Adina , Desnoyers Charlie , Hayes Kathleen , Park Ju Nyeong
Published: June 2024

Background

Fentanyl test strips (FTS) are lateral flow immunoassay strips designed for detection of ng/mL levels of fentanyl in urine. In 2021, the US Centers for Disease Control and the Substance Abuse and Mental Health Administration stated that federal funds could be used for procurement of FTS for harm reduction strategies approved by the government such as drug checking. The market for FTS has expanded rapidly in the US and Canada. However, there is no regulatory oversight by either government to ensure proper function of FTS that are being marketed for drug checking.

Main body

Many brands of FTS have rapidly entered the harm reduction market, creating concerns about the reproducibility and accuracy of their performance from brand to brand and lot to lot. Some examples are provided in this Comment. Similar problems with product quality were observed in the mid 2000’s when lateral flow immunoassays for malaria were funded in many countries and again in 2020, when COVID-19 tests were in huge demand. The combination of high demand and low levels of regulation and enforcement led some manufacturers to join the goldrush without adequate field testing or quality assurance. We argue that the harm reduction community urgently needs to set a lot checking program in place. A set of simple protocols for conducting the tests and communicating the results have been developed, and are described in the following Perspectives paper in this issue.

Conclusion

In the absence of governmental regulation and enforcement, the harm reduction community should implement a FTS lot checking program. Based on previous experience with the malaria diagnostic lot checking program, this inexpensive effort could identify products that are not suitable for harm reduction applications and provide valuable feedback to manufacturers. Dissemination of the results will help harm reduction organizations to ensure that FTS they use for drug checking are fit for the purpose.
Gut microbiota-derived acetate attenuates lung injury induced by influenza infection via protecting airway tight junctions
Authors: Hu Lei , Sun Li , Yang Chun , Zhang Da-Wei , Wei Yuan-Yuan , Yang Ming-Ming , Wu Hui-Mei , Fei Guang-He
Published: June 2024

Background

Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV) infection, suggesting the involvement of the gut-to-lung axis in a host’s response to IAV. IAV primarily destroys airway epithelium tight junctions (TJs) and consequently causes acute respiratory disease syndrome. It is known that GM and their metabolism produce an anti-influenza effect, but their role in IAV-induced airway epithelial integrity remains unknown.

Methods

A mouse model of IAV infection was established. GM were analyzed using 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) levels were measured. GM depletion and fecal microbiota transplantation (FMT) were conducted to validate the role of GM in IAV infection. A pair-feeding experiment was conducted to reveal whether IAV-induced GM dysbiosis is attributed to impaired food intake. Furthermore, human bronchial epithelial (HBE) cells were cocultured with IAV in the presence or absence of acetate. TJs function was analyzed by paracellular permeability and transepithelial electronic resistance (TEER). The mechanism of how acetate affects TJs integrity was evaluated in HBE cells transfected with G protein-coupled receptor 43 (GPR43) short hairpin RNA (shRNA).

Results

IAV-infected mice exhibited lower relative abundance of acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) and decreased acetate levels in gut and serum. These changes were partly caused by a decrease in food consumption (due to anorexia). GM depletion exacerbated and FMT restored IAV-induced lung inflammatory injury. IAV infection suppressed expressions of TJs (occludin, ZO-1) leading to disrupted airway epithelial barrier function as evidenced by decreased TEER and increased permeability. Acetate pretreatment activated GPR43, partially restored IAV-induced airway epithelial barrier function, and reduced inflammatory cytokines levels (TNF-α, IL-6, and IL-1β). Such protective effects of acetate were absent in HBE cells transfected with GPR43 shRNA. Acetate and GPR43 improved TJs in an AMP-activated protein kinase (AMPK)-dependent manner.

Conclusion

Collectively, our results demonstrated that GM protected airway TJs by modulating GPR43-AMPK signaling in IAV-induced lung injury. Therefore, improving GM dysbiosis may be a potential therapeutic target for patients with IAV infection.
Cystatin F attenuates neuroinflammation and demyelination following murine coronavirus infection of the central nervous system
Authors: Syage Amber R. , Pachow Collin , Murray Kaitlin M. , Henningfield Caden , Fernandez Kellie , Du Annie , Cheng Yuting , Olivarria Gema , Kawauchi Shimako , MacGregor Grant R. , Green Kim N. , Lane Thomas E.
Published: June 2024

Background

Cystatin F is a secreted lysosomal cysteine protease inhibitor that has been implicated in affecting the severity of demyelination and enhancing remyelination in pre-clinical models of immune-mediated demyelination. How cystatin F impacts neurologic disease severity following viral infection of the central nervous system (CNS) has not been well characterized and was the focus of this study. We used cystatin F null-mutant mice (Cst7-/-) with a well-established model of murine coronavirus-induced neurologic disease to evaluate the contributions of cystatin F in host defense, demyelination and remyelination.

Methods

Wildtype controls and Cst7-/- mice were intracranially (i.c.) infected with a sublethal dose of the neurotropic JHM strain of mouse hepatitis virus (JHMV), with disease progression and survival monitored daily. Viral plaque assays and qPCR were used to assess viral levels in CNS. Immune cell infiltration into the CNS and immune cell activation were determined by flow cytometry and 10X genomics chromium 3’ single cell RNA sequencing (scRNA-seq). Spinal cord demyelination was determined by luxol fast blue (LFB) and Hematoxylin/Eosin (H&E) staining and axonal damage assessed by immunohistochemical staining for SMI-32. Remyelination was evaluated by electron microscopy (EM) and calculation of g-ratios.

Results

JHMV-infected Cst7-/- mice were able to control viral replication within the CNS, indicating that cystatin F is not essential for an effective Th1 anti-viral immune response. Infiltration of T cells into the spinal cords of JHMV-infected Cst7-/- mice was increased compared to infected controls, and this correlated with increased axonal damage and demyelination associated with impaired remyelination. Single-cell RNA-seq of CD45 + cells enriched from spinal cords of infected Cst7-/- and control mice revealed enhanced expression of transcripts encoding T cell chemoattractants, Cxcl9 and Cxcl10, combined with elevated expression of interferon-g (Ifng) and perforin (Prf1) transcripts in CD8 + T cells from Cst7-/- mice compared to controls.

Conclusions

Cystatin F is not required for immune-mediated control of JHMV replication within the CNS. However, JHMV-infected Cst7-/- mice exhibited more severe clinical disease associated with increased demyelination and impaired remyelination. The increase in disease severity was associated with elevated expression of T cell chemoattractant chemokines, concurrent with increased neuroinflammation. These findings support the idea that cystatin F influences expression of proinflammatory gene expression impacting neuroinflammation, T cell activation and/or glia cell responses ultimately impacting neuroinflammation and neurologic disease.
PD-L1 expression in ovarian clear cell carcinoma using the 22C3 pharmDx assay
Authors: Gao Yike , Pan Boju , Jia Hongbao , Zhang Yang , Wang Shu , Wang Yuming , Zhang Sumei , Li Mei , Wang Anqi , Wang Xiaoxi , Zhao Kun , Zhang Zixin , Sun Jian , Guo Dan , Liang Zhiyong
Published: June 2024

Background

Ovarian clear cell carcinoma (OCCC), well known for its chemoresistance to platinum-based chemotherapy, exhibited a good response in clinical trials of anti–PD-1/PD-L1 inhibitors. By assessing PD-L1 expression, we sought to determine the potential therapeutic benefit of PD-1/PD-L1 inhibitors in OCCC.

Methods and results

The retrospective study included 152 individuals with OCCC between 2019 and 2022 at Peking Union Medical College Hospital. Paired tumors of primary versus recurrent lesions (17 pairs from 15 patients) or primary versus metastatic lesions (11 pairs from 9 patients) were also included. The 22C3 pharmDx assay and whole sections were used for PD-L1 immunohistochemical staining. Pathologists with experience in premarket clinical trials evaluated PD-L1 expression based on various diagnostic criteria (TPS 1%, CPS 1, or CPS 10). The number and percentage of positive PD-L1 cases were 34 (22.4%, TPS ≥ 1%) and 59 (38.8%, CPS ≥ 1), respectively. Thirty-three (21.7%) of the cases had high PD-L1 expression (CPS ≥ 10). Half of the platinum-resistant patients (11/22) were PD-L1 positive (CPS ≥ 1). In addition, positive PD-L1 expression (CPS ≥ 1) was related to clinicopathological characteristics that represented a worse prognosis, such as advanced stages, lymph node metastasis, and distant metastasis (p = 0.032, p < 0.001 and p = 0.003, separately). PD-L1 was expressed equally or more in the recurrent lesion compared with its matched primary lesion.

Conclusions

In conclusion, anti–PD-1/PD-L1 inhibitors are a promising therapeutic choice for OCCC. For evaluation of PD-L1 expression, CPS is more recommended than TPS. Evaluation of recurrent lesion was still suitable and predictive when the primary tumor tissue was not available. Distant metastatic lesions can serve as alternative samples for PD-L1 evaluation, while usage of lymphatic metastatic lesions is not recommended.
Evaluating the accuracy of a new robotically assisted system in cadaveric total knee arthroplasty procedures
Authors: Yi Jiafeng , Gao Zhisen , Huang Yijian , Liu Yubo , Zhang Yiling , Chai Wei
Published: June 2024

Background

Robot-assisted total knee arthroplasty (TKA) has been shown to facilitate high-precision bone resection, which is an important goal in TKA. The aim of this cadaveric study was to analyze the accuracy of the target angle and bone resection thickness of a recently introduced robotic TKA system.

Methods

This study used 4 frozen cadaveric specimens (8 knees), 2 different implant designs, navigation, and a robotic system. The 4 surgeons who participated in this study were trained and familiar with the basic principles and operating procedures of this system. The angle of the bone cuts performed using the robotic system was compared with the target angles from the intraoperative plan. For each bone cut, the resection thickness was recorded and compared with the planned resection thickness.

Results

The mean angular difference for all specimens was less than 1°, and the standard deviation was less than 2°. The mean difference between the planned and measured angles was close to 0 and not significantly different from 0 except for the difference in the frontal tibial component angle, which was 0.88°. The mean difference in the hip-knee-ankle axis angle was − 0.21°± 1.06°. The mean bone resection difference for all specimens was less than 1 mm, and the standard deviation was less than 0.5 mm.

Conclusions

The results of the cadaveric experimental study showed that the new TKA system can realize highly accurate bone cuts and achieve planned angles and resection thicknesses. Despite the limitations of small sample sizes and large differences between cadaveric and clinical patients, the accuracy of cadaveric experiments provides strong support for subsequent clinical trials.
Medial cortical bone thickness of the tibial diaphysis in osteoarthritis is related to lower extremity alignment and tibial morphology
Authors: Maeda Keisuke , Mochizuki Tomoharu , Tanifuji Osamu , Katsumi Ryota , Kobayashi Koichi , Kawashima Hiroyuki
Published: June 2024

Background

The purpose of this study was to clarify (1) the differences in cortical bone thickness (CBT) of the tibial diaphysis between healthy and osteoarthritic knees and (2) the influences of the femorotibial angle (FTA) and inclination of the medial compartment of the proximal tibia (MCT) on tibial CBT.

Methods

The study assessed 60 subjects with varus knee osteoarthritis (OA) (22 males and 38 females; mean age, 74 ± 7 years) and 53 healthy elderly subjects (28 males and 25 females; mean age, 70 ± 6 years). Three-dimensional estimated CBT of the tibial diaphysis was automatically calculated for 2752–11,296 points using high-resolution measurements from CT. The standardized CBT was assessed in 24 regions by combining six heights and four areas. Additionally, the association between the CBT, each FTA, and MCT inclination was investigated.

Results

The OA group showed a thicker CBT in the medial areas than in the lateral areas of the proximal tibia, while the healthy group had a thicker lateral CBT. The medial-to-lateral ratio of the proximal tibia was significantly higher in the OA group than in the healthy group. The proximal-medial CBT correlated with FTA and MCT inclinations in the OA group.

Conclusions

This study demonstrated that varus osteoarthritic knees showed a different trend of proximal-medial CBT with associations in FTA and MCT inclination from healthy knees, possibly due to medial load concentration.
Chemogenetic activation of histamine neurons promotes retrieval of apparently lost memories
Authors: Yokoi Yuto , Kubo Ayame , Nishimura Kyoka , Takamura Yuki , Morishita Yoshikazu , Minami Masabumi , Nomura Hiroshi
Published: June 2024

Memory retrieval can become difficult over time, but it is important to note that memories that appear to be forgotten might still be stored in the brain, as shown by their occasional spontaneous retrieval. Histamine in the central nervous system is a promising target for facilitating the recovery of memory retrieval. Our previous study demonstrated that histamine H3 receptor (H3R) inverse agonists/antagonists, activating histamine synthesis and release, enhance activity in the perirhinal cortex and help in retrieving forgotten long-term object recognition memories. However, it is unclear whether enhancing histaminergic activity alone is enough for the recovery of memory retrieval, considering that H3Rs are also located in other neuron types and affect the release of multiple neurotransmitters. In this study, we employed a chemogenetic method to determine whether specifically activating histamine neurons in the tuberomammillary nucleus facilitates memory retrieval. In the novel object recognition test, control mice did not show a preference for objects based on memory 1 week after training, but chemogenetic activation of histamine neurons before testing improved memory retrieval. This selective activation did not affect the locomotor activity or anxiety-related behavior. Administering an H2R antagonist directly into the perirhinal cortex inhibited the recovery of memory retrieval induced by the activation of histamine neurons. Furthermore, we utilized the Barnes maze test to investigate whether chemogenetic activation of histamine neurons influences the retrieval of forgotten spatial memories. Control mice explored all the holes in the maze equally 1 week after training, whereas mice with chemogenetically activated histamine neurons spent more time around the target hole. These findings indicate that chemogenetic activation of histamine neurons in the tuberomammillary nucleus can promote retrieval of seemingly forgotten object recognition and spatial memories.
A pilot study of mitochondrial genomic ancestry in admixed Brazilian patients with type 1 diabetes
Authors: Ferreira Lívia Leite , Gonçalves Anna Beatriz Rodrigues , Adiala Igor Josué Barbosa , Loiola Silvia , Dias Alessandra , Azulay Rossana Sousa , Silva Dayse Aparecida , Gomes Marília Brito
Published: June 2024

Interactions between multiple genes and environmental factors could be related to the pathogenesis of type 1 diabetes (T1D). The Brazilian population results from different historical miscegenation events, resulting in a highly diverse genetic pool. This study aimed to analyze the mtDNA of patients with T1D and to investigate whether there is a relationship between maternal ancestry, self-reported color and the presence of T1D. The mtDNA control region of 204 patients with T1D residing in three geographic regions of Brazil was sequenced following the International Society for Forensic Genetics (ISFG) recommendations. We obtained a frequency of Native American matrilineal origin (43.6%), African origin (38.2%), and European origin (18.1%). For self-declared color, 42.6% of the patients with diabetes reported that they were White, 50.9% were Brown, and 5.4% were Black. Finally, when we compared the self-declaration data with maternal ancestral origin, we found that for the self-declared White group, there was a greater percentage of haplogroups of Native American origin (50.6%); for the self-declared Black group, there was a greater percentage of African haplogroups (90.9%); and for the Brown group, there was a similar percentage of Native American and African haplogroups (42.3% and 45.2%, respectively). The Brazilian population with diabetic has a maternal heritage of more than 80% Native American and African origin, corroborating the country’s colonization history.
DNA methylation in peripheral blood is associated with renal aging and renal function decline: a national community study
Authors: Yang Po-Lung , Lai Tai-Shuan , Chou Yu-Hsiang , Lai Liang-Chuan , Lin Shuei-Liong , Chen Yung-Ming
Published: June 2024

Background

Older patients are at risk for acute kidney injury and chronic kidney disease. Age-related increases in DNA methylation at CpG islands have been linked to aging-related diseases like cancer and cardiovascular disease, but the exact causal relationship between methylation in renal aging and other kidney diseases remains unclear. This study aimed to elucidate the methylation status of peripheral blood mononuclear cells (PBMCs) in the Asian population. Using human whole blood DNA methylation analysis from the Taiwan Biobank, we included participants with both whole blood genome-wide methylation data and follow-up data on serum creatinine. We investigated hyper- and hypomethylated genes in comparison of participants with higher and lower estimated glomerular filtration (eGFR) decline rate in overall cohort as well as in comparison of old and young participants in subgroup of participants with higher eGFR decline rate. Common genes and signaling pathways in both comparative analyses were identified.

Results

Among 1587 participants in the analysis, 187 participants had higher eGFR decline rate. According to the comparison of methylation in participants with different eGFR declines and at different ages, respectively, we identified common hypermethylated genes, including DNMT3A and GGACT, as well as hypomethylated genes such as ARL6IP5, CYB5D1, BCL6, RPRD2, ZNF451, and MIAT in both participants with higher eGFR decline and those of older age. We observed associations between the methylation status of signaling pathways and aging as well as renal function decline. These pathways notably included autophagy, p38 mitogen-activated protein kinases, and sirtuins, which were associated with autophagy process and cytokine production.

Conclusions

Through methylation analysis of PBMCs, we identified genes and signaling pathways which could play crucial roles in the interplay of renal aging and renal function decline. These findings contribute to the development of novel biomarkers for identifying at-risk groups and even for therapeutic agent discovery.
ChirpPair: packet acquisition in uncoordinated access channels of Low Earth Orbit (LEO) satellite networks
Authors: Zhang Zhenghao
Published: June 2024

Low Earth Orbit (LEO) satellite networks provide global data service coverage and has become increasingly popular. Uncoordinated access channels reduce data latency in LEO networks by allowing user terminals to transmit data packets at random times to the satellite without any coordination overhead. In this paper, packet acquisition in uncoordinated access channels of LEO networks is studied and a novel solution, called ChirpPair, is proposed, with which the satellite can detect the packets as well as estimating key parameters of the packets for data demodulation. With ChirpPair, the packet preamble consists of a chirp and its conjugate, where a chirp is a complex vector with constant magnitude and linearly increasing frequency. ChirpPair adopts a multi-stage process that gradually increases the estimation accuracy of the parameters without incurring high computation complexity. ChirpPair has been demonstrated in real-world experiments with over-the-air transmissions. ChirpPair has also been evaluated by simulations with the 3GPP New Radio (NR) Non-Terrestrial Network (NTN) channel model and the results show that ChirpPair achieves high accuracy despite its low computation complexity.
Examining customer intentions to purchase intelligent robotic products and services in Taiwan using the theory of planned behaviour
Authors: Tai Yu-Hung , Nwachukwu Precious Toby T. , LePage Ben A. , Fang Wei-Ta
Published: June 2024

Background

The literature for assessing online and offline shopping behaviours that are linked to intelligent robotic goods and services is inadequate. In this study, we applied the Theory of Planned Behaviour model for guidance regarding how consumer behaviour affects their purchase intentions for intelligent robotic goods and services.

Methods

Data from 408 respondents were gathered through an online questionnaire binned into Online and Overall Shoppers, and analysed using SPSS, AMOS, and Covariance-Based Structural Equation Modelling software to evaluate the appropriateness of the measurements and to confirm data reliability, convergence, divergence, and validity. These tools were also used to track and test hypothesized relationships between the variables and model constructs used in this study.

Results and conclusions

The overarching outcomes from the data analyses indicated the Ease of Usage, Brand Perception, and Product Pricing variables causally impacted the TPB model constructs, namely Attitude, Subjective Norms, and Perceived Behaviour Control for the two populations tested with respect to their intention to purchase intelligent robotic goods and services. The reliability measurements for Ease of Usage, Brand Perception, and Product Pricing are discussed. The results are important for companies and future investors because opportunities to study the complex relationships that ultimately drive consumer behaviour and their intention to purchase intelligent robotic goods and services are provided.
Advanced RIME architecture for global optimization and feature selection
Authors: Abu Khurma Ruba , Braik Malik , Alzaqebah Abdullah , Gopal Dhal Krishna , Damaševičius Robertas , Abu-Salih Bilal
Published: June 2024

The article introduces an innovative approach to global optimization and feature selection (FS) using the RIME algorithm, inspired by RIME-ice formation. The RIME algorithm employs a soft-RIME search strategy and a hard-RIME puncture mechanism, along with an improved positive greedy selection mechanism, to resist getting trapped in local optima and enhance its overall search capabilities. The article also introduces Binary modified RIME (mRIME), a binary adaptation of the RIME algorithm to address the unique challenges posed by FS problems, which typically involve binary search spaces. Four different types of transfer functions (TFs) were selected for FS issues, and their efficacy was investigated for global optimization using CEC2011 and CEC2017 and FS tasks related to disease diagnosis. The results of the proposed mRIME were tested on ten reliable optimization algorithms. The advanced RIME architecture demonstrated superior performance in global optimization and FS tasks, providing an effective solution to complex optimization problems in various domains.
Engaging a community to focus on upper limb function in people with multiple sclerosis: the ThinkHand campaign case study
Authors: Thomson Alison , Horne Rachel , Chapman Christine , Bharadia Trishna , Burke Patrick , Colwell Elizabeth , Harrington Mark , Boskovic Bonnie , Stennett Andrea , Baker David , Giovannoni Gavin , Schmierer Klaus
Published: June 2024

Background: Solving complex research challenges requires innovative thinking and alternative approaches to traditional methods. One such example is the problem of arm and hand, or upper limb function in multiple sclerosis (MS), a neurological condition affecting approximately 2.9 million people worldwide and more than 150,000 in the United Kingdom. Historically, clinical trials and research have focused on mobility and walking ability. This excludes a large number of patients who are wheelchair users, limiting their quality of life and restricting access to possibly helpful medications. To address this issue, the ThinkHand campaign was launched in 2016, aiming to raise awareness about the importance of upper limb function in MS and develop alternative ways to measure, record, and account for hand and arm function changes.

Main body: The campaign utilised innovative strategies at scientific conferences and online surveys to engage people affected by MS, healthcare professionals, charities, and researchers in discussing the importance of preserving upper limb function. Through co-design and interdisciplinary collaboration, the campaign developed new tools like the low-cost cardboard version of the Nine-Hole Peg Test, facilitating remote monitoring of hand function. Additionally, the campaign co-created the “Under & Over” rehabilitation tool, allowing individuals with advanced MS to participate in a remote rehabilitation program.

The impact of the ThinkHand campaign has been significant, helping to shift the focus of both academic and industry-supported trials, including the O’HAND and ChariotMS trials, both using upper limb function as their primary end point. The campaign’s patient-centred approach highlighted the importance of recognising patients’ perspectives in research and challenged established assumptions and practices. It demonstrated the effectiveness of interdisciplinary collaboration, systems thinking, and co-creation with stakeholders in tackling complex problems.

Conclusion: The ThinkHand campaign provides valuable insights for health research practices. By involving patients at all stages, researchers can gain a deeper understanding of the impact of disease on their lives, identify gaps and focus research on their needs. Experimentation and iteration can lead to innovative solutions, and openness to unconventional methods can drive widespread change. The ThinkHand campaign exemplifies the potential of patient-centred approaches to address complex research challenges and revolutionise the field of MS research and management. Embracing such approaches will contribute to more inclusive and impactful research in the future.
Navigating the crossroads: cardiometabolic risks in cancer survivorship – a comprehensive review
Authors: Albulushi Arif , Balushi Aisha Al , Shahzad Muhhamed , Bulushi Ismail Al , Lawati Hatim Al
Published: June 2024

The landscape of cancer survivorship is increasingly populated by individuals facing a spectrum of cardiometabolic risks, attributed to both their oncological history and treatment regimens. This manuscript synthesizes findings from various studies, highlighting the prevalence of traditional risk factors—hypertension, dyslipidemia, diabetes—as well as emergent concerns like obesity and metabolic syndrome among survivors. The impact of demographic variables, specific cancer types, and treatment modalities on cardiometabolic health is explored. Through a lens of multidisciplinary management and future research directives, we advocate for an integrative approach to cardiometabolic health in cancer survivors, aiming to ensure their victory over cancer extends into long-term well-being.

Graphical Abstract
Associations between body composition and intradialytic hypotension (IDH), and between IDH and prognosis, in hemodialysis patients
Authors: Mizuiri Sonoo , Nishizawa Yoshiko , Doi Toshiki , Okubo Aiko , Morii Kenichi , Yamashita Kazuomi , Suga Yukari , Usui Koji , Shigemoto Kenichiro , Masaki Takao
Published: June 2024

Background

Previous studies describing relationships among body compositions, intradialytic hypotension (IDH), and mortality yielded inconsistent results. We studied associations between body composition and IDH, and between IDH and prognosis, in patients on hemodialysis (HD).

Methods

Participants were patients on maintenance HD and predilution online hemodiafiltration (HDF) (n = 303). IDH was defined as nadir systolic blood pressure (SBP) < 90 mmHg for ≥ 2 of 10 dialysis sessions during the exposure period (days 1–22). Clinical data at day 1 and post-dialysis body compositions using bioelectrical impedance analysis conducted once during the exposure period were collected. Differences between the IDH and non-IDH groups were analyzed. Kaplan–Meier survival curves of the IDH and non-IDH groups, logistic regression analyses of IDH, and Cox proportional hazard analyses of all-cause and cardiovascular (CV) mortality in all participants were also performed.

Results

In all participants, the median (median [interquartile range]) age was 67 [56–74] years, median dialysis duration was 76 [37–145] months, and diabetes prevalence was 42.6% (129/303). Compared with the non-IDH group (n = 274), the IDH group (n = 29) had a lower mean pre-dialysis SBP during the exposure period, longer dialysis duration, lower serum albumin levels, and higher median fat tissue index (10.7 [8.6–14.9] versus 9.5 [6.8–11.9] kg/m2, P < 0.05). The IDH group had lower 3-year survival for all-cause and CV mortality (P < 0.05). When adjusted for mean pre-dialysis SBP, mean ultrafiltration volume during the exposure period, HDF, dialysis duration, and serum albumin, fat tissue index, and lean tissue index were associated with IDH (P < 0.05), but body mass index and overhydration/extracellular water were not. After additional adjustments for age, sex, and diabetes mellitus, only fat tissue index was a significant predictor for IDH [odds ratio: 1.12 (95% confidence interval 1.02–1.25), P < 0.05]. IDH was also a significant predictor of 3-year all-cause and CV mortality (P < 0.05).

Conclusions

Increased fat tissue index was a significant risk factor for IDH in HD and HDF patients. Furthermore, IDH was a significant predictor of 3-year all-cause and CV mortality in HD and HDF patients.
The use of Efficientnet_b0 network to identify COVID-19 in chest X-ray images
Authors: Ayitey Junior Michael , Appiahene Peter , Missah Yaw Marfo , Akoto-Adjepong Vivian
Published: June 2024

A newly discovered coronavirus called COVID-19 poses the greatest threat to mankind in the twenty-first century. Mortality has dramatically increased in all cities and countries due to the virus's current rate of spread. A speedy and precise diagnosis is also necessary in order to treat the illness. This study identified three groups for chest X-ray images: Covid, normal, and pneumonia. This study's objective is to present a framework for categorizing chest X-ray images into three groups of pneumonia, normal, and Covid scenarios. To do this, chest X-ray images from the Kaggle database which have been utilized in previous studies were obtained. It is suggested to use an Efficientnet_b0 model to identify characteristics in raw data hierarchically. An unedited X-ray image of the chest is enhanced for more reasonable assumptions in order to apply the proposed method in real-world situations. With an overall accuracy of 93.75%, the proposed network correctly identified the chest X-ray images to the classes of Covid, viral pneumonia, and normal on the test set. 90% accuracy rate for the test dataset was attained for the viral pneumonitis group. On the test dataset, the Normal class accuracy was 94.7%, while the Covid class accuracy was 96%. The findings indicate that the network is robust. In addition, when compared to the most advanced techniques of identifying pneumonia, the concluded findings from the suggested model are highly encouraging. Since the recommended network is successful at doing so utilizing chest X-ray imaging, radiologists can diagnose COVID-19 and other lung infectious infections promptly and correctly.
Postmarketing Safety Concerns of Teprotumumab: A Real-World Pharmacovigilance Assessment
Authors: Huang Jing , Su Anping , Yang Jing , Zhuang Wei , Li Zhihui
Published: June 2024

Context

Teprotumumab, which targets the insulin-like growth factor-1 receptor, is the only drug approved by the US Food and Drug Administration (FDA) for the treatment of thyroid eye disease (TED).

Objective

This study aimed to identify potential safety signals of teprotumumab by analyzing postmarketing safety data from the FDA Adverse Event Reporting System (FAERS) database in 2023.

Methods

The case/noncase approach was used to estimate the reporting odds ratio (ROR) and information component (IC) with relevant 95% CI for adverse events (AEs) that numbered 3 or more.

Results

A total of 2158 cases were included in the analysis. Main safety signals identified were ear and labyrinth disorders, reproductive system and breast disorders, metabolism and nutrition disorders, and gastrointestinal disorders. Specifically, autophony (ROR [95% CI] = 4188.34 [1403.29-12500.8]), eyelid retraction (ROR [95% CI] = 2094.17 [850.69-5155.29]), permanent deafness (ROR [95% CI] = 1552.35 [789.07-3053.98]), bilateral deafness (ROR [95% CI] = 73.12 [41.14-129.97]), inflammatory bowel disease (ROR [95% CI] = 23.26 [13.46-40.19]), hyperglycemic hyperosmolar nonketotic syndrome (ROR [95% CI] = 17.75 [5.70-55.28]), and amenorrhea (ROR [95% CI] = 47.98 [36.22-63.54]) showed significant safety signals with teprotumumab.

Conclusion

This study identified ear and labyrinth disorders, and reproductive system and breast disorders, as specific safety signals of teprotumumab. Clinicians and pharmacists should be vigilant regarding these AEs. However, available data are currently insufficient, and further pharmacovigilance and surveillance are needed to fully understand this issue.
The Clarifying Hackathon in Health Profession Education
Authors: Rooholamini Azadeh , Sarfraz Khan Junaid , Rezaei-Gazki Parvin , Salajegheh Mahla
Published: June 2024

doi: https://doi.org/10.12669/pjms.40.7.10104
How to cite this: Rooholamini A, Khan JS, Rezaei-Gazki P, Salajegheh M. Clarifying Hackathon in Health Profession Education. Pak J Med Sci. 2024;40(7):---------. doi: https://doi.org/10.12669/pjms.40.7.10104
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.