bluuebunny/crossref_metadata_2025 huggingface dataset:
Can regulatory T cells improve outcomes of sensitised patients after HLA-Ab incompatible renal transplantation: study protocol for the Phase IIa GAMECHANgER-1 trial
Authors: Dudreuilh C , Jarvis P , Beadle N , Pilecka I , Shaw O , Gardner L , Scottà C , Mamode N , Game DS , Sanchez-Fueyo A , Lombardi G , Learoyd A , Douiri A , Dorling A
Published: April 2023

Background

Kidney transplantation is the gold-standard treatment for patients with kidney failure. However, one-third of patients awaiting a kidney transplant are highly sensitized to human leukocyte antigens (HLA), resulting in an increased waiting time for a suitable kidney, more acute and chronic rejection, and a shorter graft survival compared to non-highly sensitised patients. Current standard immunosuppression protocols do not adequately suppress memory responses, and so alternative strategies are needed. Autologous polyclonally expanded regulatory T cells (Tregs) have been demonstrated to be safe in transplant settings and could be a potential alternative to modulate memory immune alloresponses.

Methods

The aim of this trial is to determine whether adoptive transfer of autologous Tregs into HLA sensitised patients can suppress memory T and B cell responses against specific HLA antigens. This is a two-part, multi-centre, prospective clinical trial, comprising an observational phase (Part 1) aiming to identify patients with unregulated cellular memory responses to HLA (Pure HLA Proteins) followed by an interventional phase (Part 2). The first 9 patients identified as being eligible in Part 1 will undergo baseline immune monitoring for 2 months to inform statistical analysis of the primary endpoint. Part 2 is an adaptive, open labelled trial based on Simon’s two-stage design, with 21 patients receiving Good Manufacturing Practice (GMP)-grade polyclonally expanded Tregs to a dose of 5–10 × 106 cells/kg body weight. The primary EP is suppression of in vitro memory responses for 2 months post-infusion. 12 patients will receive treatment in stage 1 of Part 2, and 9 patients will receive treatment in stage 2 of Part 2 if ≥ 50% patients pass the primary EP in stage 1.

Discussion

This is a prospective study aiming to identify patients with unregulated cellular memory responses to Pure HLA Proteins and determine baseline variation in these patterns of response. Part 2 will be an adaptive phase IIa clinical trial with 21 patients receiving a single infusion of GMP-grade polyclonally expanded Tregs in two stages. It remains to be demonstrated that modulating memory alloresponses clinically using Treg therapy is achievable.

Trial registration

EudraCT Number: 2021–001,664-23.

REC Number: 21/SC/0253.

Trial registration number ISRCTN14582152.
Papilledema and venous stasis in patients with cerebral venous and sinus thrombosis
Authors: Park Min-Gyu , Roh Jieun , Ahn Sung-Ho , Park Kyung-Pil , Baik Seung Kug
Published: April 2023

Background

Cerebral venous and sinus thrombosis (CVST) can cause increased intracranial pressure, often leading to papilledema. In this study, we investigated the association between papilledema and venous stasis on susceptibility weighted imaging (SWI) in CVST.

Methods

Patients with CVST between 2008 and 2020 were reviewed. Patients without fundoscopic examination or SWI were excluded in this study. Venous stasis was evaluated and scored for each cerebral hemisphere: each hemisphere was divided into 5 regions according to the venous drainage territories (superior sagittal sinus, Sylvian veins, transverse sinus and vein of Labbé, deep cerebral veins, and medullary veins) and 1 point was added if venous prominence was confirmed in one territory on SWI. The venous stasis score on SWI between cerebral hemispheres with and without papilledema was compared.

Results

Eight of 19 patients with CVST were excluded because of the absence of fundoscopic examination or SWI. Eleven patients (26.5 ± 2.1 years) were included in this study. Papilledema was identified in 6 patients: bilateral papilledema in 4 patients and unilateral papilledema in 2 patients. The venous stasis score on SWI was significantly higher (P = 0.013) in the hemispheres with papilledema (median, 4.0; 95% CI, 3.038–4.562) than in the hemispheres without papilledema (median, 2.5; 95% CI, 0.695–2.805).

Conclusions

This study shows that higher score of venous stasis on SWI is associated with papilledema. Therefore, the venous stasis on SWI may be an imaging surrogate marker of increased intracranial pressure in patients with CVST.
Measurement invariance of the PHQ-9 and GAD-7 across males and females seeking treatment for common mental health disorders
Authors: Saunders Rob , Moinian Delilah , Stott Joshua , Delamain Henry , Naqvi Syed Ali , Singh Satwant , Wheatley Jon , Pilling Stephen , Buckman Joshua E.J.
Published: April 2023

Background

The nine-item Patient Health Questionnaire (PHQ-9) and the seven-item Generalised Anxiety Disorder scale (GAD-7) are routinely used in research and clinical practice. Whilst measurement invariance of these measures across gender has been demonstrated individually in general population studies and clinical samples, less is known about invariance of the distinct but correlated latent factors (‘depression’ and ‘anxiety’). The current study assessed measurement invariance of these constructs across males and females seeking treatment for common mental health disorders.

Methods

Data were provided from eight psychological treatment services in London, England. Data from initial assessments with the services where individual items on the PHQ-9 and GAD-7 were available were included in analyses. Measurement invariance was explored across self-identified genders, with ‘male’ and ‘female’ categories available in the dataset. Sensitivity analyses were conducted using propensity score matching on sociodemographic and clinical variables.

Results

Data were available for 165,872 patients (110,833 females, 55,039 males). There was evidence of measurement invariance between males and females in both the full sample and a propensity score matched sample (n = 46,249 in each group).

Conclusions

Measurement invariance of the correlated depression and anxiety factors of PHQ-9 and GAD-7 were indicated in this sample of individuals seeking psychological treatment for CMHDs. These results support the use of these measures in routine clinical practice for both males and females. This is of particular importance for assessing the prevalence of clinically significant levels of symptoms as well as comparing treatment outcomes across genders.
Perceptions of plain packaging and health warnings among university students in Turkey: a survey-based experiment
Authors: Caner Asena , Turan Belgi , Gürdal Mehmet Y. , Güven Sibel
Published: April 2023

Background

Cigarette pack design plays a crucial role in attracting customers, especially when other marketing methods are limited by policy. University students who engage in casual smoking take the risk of developing an addiction. The objective of this study was to assess the effects of plain packaging (PP) and graphic health warnings (GHWs) on cigarette packages on three outcome variables (negative affect, avoidant responses, and intentions to quit) among ever-smoker university students in Ankara, Turkey, where youth smoking prevalence is high.

Methods

An online survey-based experiment was used to collect data. The respondents were randomly assigned to one of the five conditions that contained images of cigarette packs with specific design elements. Regression analyses (n = 623) were used to compare across conditions and to estimate the effects of combined warnings (versus text-only warnings), stronger GHWs (versus old GHWs), and PP (versus branded packages) on the outcome variables, accounting for potential confounders.

Results

Stronger GHWs generated more negative affect (0.31 points out of 5, p = 0.010) and avoidant responses (0.42 points out of 5, p = 0.002) than old warnings (when brand logos were visible). Plain packages generated more negative affect (0.48 points out of 5, p < 0.001) and avoidant responses (0.46 points out of 5, p = 0.001) than branded packages (with old warnings). Disentangling the effects of PP and new GHWs revealed that neither had individual differential effect on intentions to quit within 6 months.

Conclusions

Although no differential effect of PP or harsher GHWs was found on intentions to quit when respondents were exposed to images on screen, both design elements were found to be effective in generating negative affect and avoidant responses. More work is needed to design effective tobacco control measures among youth during critical years of tertiary education.
Association between maternal marginalization and infants born with congenital heart disease in Ontario Canada
Authors: Miao Qun , Dunn Sandra , Wen Shi Wu , Lougheed Jane , Yang Phoebe , Davies Michael , Venegas Carolina Lavin , Walker Mark
Published: April 2023

Background

This study aims to evaluate the impact of socioeconomic status (SES) on the risk of congenital heart disease (CHD) since previous studies have yielded inconsistent results.

Methods

We conducted a population-based retrospective cohort study, including all singleton live and still births in Ontario hospitals from April 1, 2012, to March 31, 2018. We used linked records from the Better Outcomes Registry & Network Information System, the Canadian Institute for Health Information databases, and the Ontario Marginalization Index (ON_Marg). ON_Marg was estimated at a dissemination area level using Canadian Census 2016 data and categorized into quintiles. Multivariable logistic regression models were performed to examine the relationships between four ON_Marg indices (material deprivation, dependency, ethnic concentration, residential instability), as proxies for maternal SES and the risk of infant CHD. We adjusted for maternal age at birth, assisted reproductive technology, obesity, pre-existing health conditions, substance use during pregnancy, mental health conditions before and during pregnancy, rural residence, and infant’s sex in the analysis.

Results

Among the cohort of 776,799 singletons, 9,359 infants had a diagnosis of CHD. Of those, 3,069 were severe CHD and 493 cases were single ventricle CHD. The prevalence of all infant CHD types was higher for males relative to females. Compared to mothers living in neighbourhoods with the lowest material deprivation, mothers with highest material deprivation had a 27% (adjusted OR = 1.27; 95% CI: 1.18–1.37) higher odds of having an infant diagnosed with CHD. Mothers living in neighbourhoods with the highest minority ethnic and immigrant concentration tend to have infants with 11% lower odds of CHD (adjusted OR = 0.89; 95% CI: 0.82–0.97) as compared to those living in the least ethnically diverse communities. Maternal dependency and residential stability quintiles were not significantly associated with the risk of CHD.

Conclusion

Higher maternal material deprivation was associated with increasing odds of infant CHD, whereas neighbourhood minority ethnic concentration was inversely associated with the odds of infant CHD. Our study further confirms that poverty is associated with CHD development. Future investigations might focus on the causal pathways between social deprivation, immigrant status, ethnicity, and the risk of infant CHD.
Musculoskeletal pain latent classes and biopsychosocial characteristics among emerging adults
Authors: Gallagher Kaitlin M. , Howie Erin K. , Carney Makayla
Published: April 2023

Background

Emerging adults (aged 18–29) report high levels of musculoskeletal pain; however, it is unknown if body location and intensity patterns are related to different biopsychosocial characteristics. This study identified patterns of self-reported musculoskeletal pain among emerging adults and assessed if there were differences in their lifestyle and psychological characteristics.

Methods

Data from survey responses from a large public university and a large medical university in the United States were used (n = 1,318). Self-reported pain location and intensity at five body regions were assessed, and latent class analysis identified classes separately for men and women. Mental health, physical activity, and sleep outcomes were compared between the classes.

Results

Four classes were identified for men and women. Three of the classes were consistent between genders – “no pain,” (women = 28% of their sample; men = 40% of their sample) “mild multisite pain,” (women = 50%; men = 39%) and “moderate-severe multisite pain” (women = 9%; men = 7%). The fourth class for women was “moderate spine pain,” (13%) and for men was “mild extremity pain” (13%). For both men and women, the “moderate-severe multisite” pain classes reported the highest levels of depression, anxiety, and stress, poorer sleep, and higher work physical activity than the “no pain” class. The “mild multisite” and “moderate spine” (women only) pain classes fell between the “no pain” and “moderate-severe” pain classes. The characteristics of the “mild upper extremity pain” class for men was similar to the “no pain” class.

Conclusions

The identified classes provide unique information on pain location and intensity in emerging adults. The high prevalence of “mild multisite pain” (n = 593; 45% of the total sample) demonstrates an intervention opportunity during this age range to prevent further increases in musculoskeletal pain later in life. Future work should assess the longitudinal outcomes of these pain classes, the impact of interventions for this age group, and the balance between leisure and occupational physical activity when addressing musculoskeletal health.
Long-term results for pit-picking and flap procedures in primary pilonidal sinus disease
Authors: Koskinen K. , Harju J. , Hermunen K.
Published: April 2023

Background

Pilonidal sinus disease (PSD), a common inflammatory condition of the natal cleft causing morbidity especially in young adults, is a heterogeneous disease group with no consensus regarding its best treatment. Our aim was to report long-term results for primary PSD surgery.

Methods

We retrospectively studied the medical records of 146 patients who underwent primary PSD surgery between November 2010 and October 2015. Of these, 113 underwent either the mini-invasive pit-picking surgery (PSS) (n = 55) or asymmetrical excision with local flap (AELF) (n = 58); we focused on the outcomes of these two subgroups.

Results

PSD patients who underwent mini-invasive PPS more often succeeded with day surgery (94.5% vs 32.8%, p < 0.001), had fewer postoperative complications (9.4% vs 36.2%, p = 0.002), and had shorter sick leave (median 14 days vs 21 days, p < 0.001) than did AELF patients. Nevertheless, at the first postoperative follow-up visit, both surgery methods healed similarly (75.0% vs 76.8%, p = 0.83). Our long-term follow-up, at a median of 9.3 years (range 5.4–10.6), revealed, however, that recurrence after PPS was markedly higher than after AELF (50.9% vs 10.3%, HR 6.65, p < 0.001).

Conclusions

PPS, which is a mini-invasive surgical technique often performed under local anaesthesia, is suitable for primary PSD, despite the high recurrence rate in our study, bearing in mind that patient selection is an important factor to consider. Primary PSD with simple sinus formations may benefit from PPS. On the other hand, primary PSD with complex sinus formations may benefit from AELF regardless of the initial slow recovery in our study. Because PSD is a very heterogenous disease, and patients have different risk factors, it is mandatory for the surgeon to master several different surgical techniques. A classification system to aid the surgeon in selecting the right surgical technique for each patient is warranted.
Kinetically and thermodynamically controlled one-pot growth of gold nanoshells with NIR-II absorption for multimodal imaging-guided photothermal therapy
Authors: Chen Ming , Chen Xiao-Tong , Zhang Lian-Ying , Meng Wei , Chen Yong-Jian , Zhang Ying-Shan , Chen Zhi-Cong , Wang Hui-Min , Luo Chun-Mei , Shi Xiu-Dong , Zhang Wen-Hua , Wang Mao-Sheng , Chen Jin-Xiang
Published: April 2023

Since the successful clinical trial of AuroShell for photothermal therapy, there is currently intense interest in developing gold-based core-shell structures with near-infrared (NIR) absorption ranging from NIR-I (650–900 nm) to NIR-II (900–1700 nm). Here, we propose a seed-mediated successive growth approach to produce gold nanoshells on the surface of the nanoscale metal–organic framework (NMOF) of UiO-66-NH2 (UiO = the University of Oslo) in one pot. The key to this strategy is to modulate the proportion of the formaldehyde (reductant) and its regulator / oxidative product of formic acid to harness the particle nucleation and growth rate within the same system. The gold nanoshells propagate through a well-oriented and controllable diffusion growth pattern (points → facets → octahedron), which has not been identified. Most strikingly, the gold nanoshells prepared hereby exhibit an exceedingly broad and strong absorption in NIR-II with a peak beyond 1300 nm and outstanding photothermal conversion efficiency of 74.0%. Owing to such superior performance, these gold nanoshells show promising outcomes in photoacoustic (PA), computed tomography (CT), and photothermal imaging-guided photothermal therapy (PTT) for breast cancer, as demonstrated both in vitro and in vivo.
The intratumour microbiota and neutrophilic inflammation in squamous cell vulvar carcinoma microenvironment
Authors: Rustetska Natalia , Szczepaniak Magdalena , Goryca Krzysztof , Bakuła-Zalewska Elwira , Figat Małgorzata , Kowalik Artur , Góźdź Stanisław , Kowalewska Magdalena
Published: April 2023

Background

A causal link between microbiota composition (dysbiosis) and oncogenesis has been demonstrated for several types of cancer. Neutrophils play a role in both immune protection against bacterial threats and carcinogenesis. This study aimed to characterise intratumoral bacteria in vulvar squamous cell carcinoma (VSCC) and their putative effect on neutrophil recruitment and cancer progression.

Methods

Clinical material was obtained from 89 patients with VSCC. Next-generation sequencing (NGS) of 16S rRNA and quantitative polymerase chain reaction (qPCR) were used to detect bacterial species in VSCC. To verify neutrophil activation, CD66b expression in tumour specimens was analysed by immunohistochemistry (IHC). Subsequently, IHC was applied to detect the main neutrophil serine proteases (NSPs), cathepsin G (CTSG), neutrophil elastase (ELANE), and proteinase 3 (PRTN3) in VSCC.

Results

Fusobacterium nucleatum and Pseudomonas aeruginosa were identified as tumour-promoting bacteria, and their presence was found to be associated with a shorter time to progression in VSCC patients. Furthermore, high abundance of CD66b, the neutrophil activation marker, in VSCC samples, was found to relate to poor survival of patients with VSCC. The selected NSPs were shown to be expressed in vulvar tumours, also within microabscess. The increased numbers of microabscesess were correlated with poor survival in VSCC patients.

Conclusions

Our results show that neutrophilic inflammation seem to be permissive for tumour-promoting bacteria growth in VSCC. The findings provide new therapeutic opportunities, such as based on shifting the balance of neutrophil populations to those with antitumorigenic activity and on targeting NSPs produced by activated neutrophils at the inflammation sites.
Single-direction thoracoscopic lobectomy for children with congenital lung malformation: initial experience
Authors: Huang Jin-Xi , Chen Qiang , Hong Song-Ming , Hong Jun-Jie , Cao Hua
Published: April 2023

Background

Thoracoscopic lobectomy is a common treatment for congenital lung malformation. Single-direction thoracoscopic lobectomy may be an effective and safe approach without the need to flip the lung over repeatedly, thus minimizing tissue trauma, but its use has not been reported in children. The purpose of this study was to evaluate the safety and efficacy of single-direction thoracoscopic lobectomy in children.

Methods

A total of 91 patients who underwent thoracoscopic lobectomy in our hospital from January 2020 to December 2020 were retrospectively analysed. According to the inclusion criteria, 21 children were identified as the single-direction group. The details of the single-direction thoracoscopic lobectomy technique are described. Another 21 patients who underwent conventional thoracoscopic lobectomy in the same period were matched using the propensity score matching and set as the control group, the clinical outcomes between the two groups were compared.

Results

The median age of the patients was 4.72 months (4.72 ± 0.90) with a mean body weight of 7.43 kg (7.43 ± 1.14). There were no significant differences in intraoperative blood loss (P = 0.549), operation time (P = 0.859), length of chest tube drainage (P = 0.102) and length of hospital stay (P = 0.636) between the 2 groups. No patients experienced bronchopleural fistula and conversion to thoracotomy in either group. All patients recovered well without respiratory symptoms or other complications after follow-up of more than 1 year.

Conclusions

Our preliminary experience presented a series of single-direction video-assisted thoracoscopic lobectomy for children with satisfactory perioperative results.
ESTIMation of the ABiLity of prophylactic central compartment neck dissection to modify outcomes in low-risk differentiated thyroid cancer: a prospective randomized trial
Authors: Hartl Dana , Godbert Yann , Carrat Xavier , Bardet Stéphane , Lasne-Cardon Audrey , Vera Pierre , Ilies Elena , Zerdoud Slimane , Sarini Jérôme , Zalzali Mohamad , La Manna Luigi , Schneegans Olivier , Kelly Antony , Kauffmann Philppe , Rodien Patrice , Brunaud Laurent , Grunenwald Solange , Housseau Elie , Laghouati Salim , Bouvet Nathalie , Lecerf Elodie , Hadoux Julien , Lamartina Livia , Schlumberger Martin , Borget Isabelle
Published: April 2023

Background

Prophylactic central neck dissection in clinically low-risk cT1bT2N0 papillary thyroid carcinoma is controversial, due to a large number of conflicting retrospective studies, some showing an advantage in terms of locoregional recurrence, others showing no advantage. These previous studies all show high rates of excellent response. We aim to demonstrate the non-inferiority of thyroidectomy alone as compared to total thyroidectomy with prophylactic central neck dissection in conjunction with adjuvant RAI 30 mCi with rTSH stimulation in terms of excellent response at 1 year.

Trial design and methods

Prospective randomized open multicenter phase III trial including patients with 11–40-mm papillary thyroid carcinoma (Bethesda VI) or suspicious cytology (Bethesda V) confirmed malignant on intra-operative frozen section analysis, with no suspicious lymph nodes on a specialized preoperative ultrasound examination. Patients will be randomized 1:1 into two groups: the reference group total thyroidectomy with bilateral prophylactic central neck dissection, and the comparator group total thyroidectomy alone. All patients will receive an ablative dose of 30mCi of radioactive iodine (RAI) within 4 months of surgery. The primary outcome is to compare the rate of excellent response at 1 year after surgery between the groups, as defined by an unstimulated serum thyroglobulin (Tg) level ≤ 0.2 ng/mL with no anti-Tg antibodies, an normal neck ultrasound and no ectopic uptake on the post-RAI scintiscan. Non-inferiority will be demonstrated if the rate of patients with excellent response at 1 year after randomization does not differ by more than 5%. Setting the significance level at 0.025 (one-sided) and a power of 80% requires a sample size of 598 patients (299 per group). Secondary outcomes are to compare Tg levels at 8 +/− 2 postoperative weeks, before RAI ablation, the rate of excellent response at 3 and 5 years, the rate of other responses at 1, 3, and 5 years (biochemical incomplete, indeterminate, and structurally incomplete responses), complications, quality of life, and cost-utility.

Discussion (potential implications)

If non-inferiority is demonstrated with this high-level evidence, prophylactic neck dissection will have been shown to not be necessary in clinically low-risk papillary thyroid carcinoma.

Trial registration

NCT 03570021. June 26,2018
Partial erosion on under-methylated regions and chromatin reprogramming contribute to oncogene activation in IDH mutant gliomas
Authors: Wang Xinyu , Dai Lijun , Liu Yang , Li Chenghao , Fan Dandan , Zhou Yue , Li Pengcheng , Kong Qingran , Su Jianzhong
Published: April 2023

Background

IDH1/2 hotspot mutations are well known to drive oncogenic mutations in gliomas and are well-defined in the WHO 2021 classification of central nervous system tumors. Specifically, IDH mutations lead to aberrant hypermethylation of under-methylated regions (UMRs) in normal tissues through the disruption of TET enzymes. However, the chromatin reprogramming and transcriptional changes induced by IDH-related hypermethylation in gliomas remain unclear.

Results

Here, we have developed a precise computational framework based on Hidden Markov Model to identify altered methylation states of UMRs at single-base resolution. By applying this framework to whole-genome bisulfite sequencing data from 75 normal brain tissues and 15 IDH mutant glioma tissues, we identified two distinct types of hypermethylated UMRs in IDH mutant gliomas. We named them partially hypermethylated UMRs (phUMRs) and fully hypermethylated UMRs (fhUMRs), respectively. We found that the phUMRs and fhUMRs exhibit distinct genomic features and chromatin states. Genes related to fhUMRs were more likely to be repressed in IDH mutant gliomas. In contrast, genes related to phUMRs were prone to be up-regulated in IDH mutant gliomas. Such activation of phUMR genes is associated with the accumulation of active H3K4me3 and the loss of H3K27me3, as well as H3K36me3 accumulation in gene bodies to maintain gene expression stability. In summary, partial erosion on UMRs was accompanied by locus-specific changes in key chromatin marks, which may contribute to oncogene activation.

Conclusions

Our study provides a computational strategy for precise decoding of methylation encroachment patterns in IDH mutant gliomas, revealing potential mechanistic insights into chromatin reprogramming that contribute to oncogenesis.
Increased risk of death following recurrent ketoacidosis admissions: a Brazilian cohort study of young adults with type 1 diabetes
Authors: Santos Sarah S. , Ramaldes Luana A. L. , Dualib Patricia M. , Gabbay Monica A. L. , Sá João R. , Dib Sergio A.
Published: April 2023

Background

Recurrent DKA (rDKA) remains an acute type 1 diabetes complication even in post-insulin era. This study aimed to analyze the predictors and effects of rDKA on the mortality of patients with type 1 diabetes.

Methods

Patients hospitalized (n = 231) wih diabetic ketoacidosis (between 2007 and 2018) were included. Laboratorial and clinical variables were collected. Mortality curves were compared in four groups: diabetic ketoacidosis as a new-onset type 1 diabetes (group A), single diabetic ketoacidosis episode after diagnosis of type 1 diabetes (group B), 2–5 diabetic ketoacidosis events (group C), and > 5 diabetic ketoacidosis events during follow-up period (group D).

Results

During the follow-up period (approximately 1823 days), the mortality rate was 16.02% (37/231). The median age at death was 38.7 years. In the survival curve analysis, at 1926 days (5 years), the probabilities of death were indicated by ratios of 7.78%, 4.58%, 24.40%, and 26.63% in groups A, B, C, and D, respectively. One diabetic ketoacidosis episode compared with ≥ 2 events had a relative risk of 4.49 (p = 0.004) of death and > 5 events had 5.81 (p = 0.04). Neuropathy (RR 10.04; p < 0.001), retinopathy (relative risk 7.94; p < 0.01), nephropathy (RR 7.10; p < 0.001), mood disorders (RR 3.57; p = 0.002), antidepressant use (RR 3.09; p = 0.004), and statin use (RR 2.81; p = 0.0024) increased the risk of death.

Conclusions

Patients with type 1 diabetes with > 2 diabetic ketoacidosis episodes have four times greater risk of death in 5 years. Microangiopathies, mood disorders, and use of antidepressants and statins were important risk factors for short-term mortality.
Enteric methane output and weight accumulation of Nguni and Bonsmara cows raised under different grazing conditions
Authors: Slayi Mhlangabezi , Kayima Denis , Jaja Ishmael Festus , Mapiye Cletos , Dzama Kennedy
Published: April 2023

Several experts throughout the world have focused a lot of their research on the rise in methane concentrations in the atmosphere and its causes. Cattle are the livestock species that contribute the most to methane emissions, according to research conducted over the previous three decades. A greenhouse gas called enteric methane (CH4) is created by microbial fermentation in the rumen and is released into the atmosphere through a variety of excretory processes. To reduce methane emissions, research on the ways that various breeds of cattle are reared on different grazing regimes should be prioritized. The goal of the current study was to measure the weight gain and intestinal methane emission of Nguni and Bonsmara cows grown under various grazing conditions. Eighty-four cows belonging to the 2 grazing systems were randomly selected and grouped according to three age groups: A (young adult cow, n = 7, 24–48 months), B (adult, n = 7, 60–80 months), and C (old adult, n = 7, 90–120 months) are three different age groups for adult cows. Methane production was higher per head in older animals, with C producing the most, followed by B and A (C > B > A; P 0.0001). In Bonsmara, body condition, body weight (BW), dry matter intake (DMI), and daily methane were all higher (P 0.05). Nguni had more methane per pound of weight (P 0.05), although methane per kilogram of body mass (P > 0.05) was similar across breeds. In the commercial system, body condition, BW, and DMI were higher (P 0.05). On the other hand, communal grazing resulted in increased daily methane production, methane per DMI, and methane produced per BW. These findings support the notion that breed genetics, grazing system, and age all have an impact on methane levels and performance. So, all these aspects must be taken into account in breeding strategies for traits like methane production that are challenging to assess.
Microglial CD68 and L-ferritin upregulation in response to phosphorylated-TDP-43 pathology in the amyotrophic lateral sclerosis brain
Authors: Swanson Molly E. V. , Mrkela Miran , Murray Helen C. , Cao Maize C. , Turner Clinton , Curtis Maurice A. , Faull Richard L. M. , Walker Adam K. , Scotter Emma L.
Published: April 2023

Microglia, the innate immune cells of the brain, are activated by damage or disease. In mouse models of amyotrophic lateral sclerosis (ALS), microglia shift from neurotrophic to neurotoxic states with disease progression. It remains unclear how human microglia change relative to the TAR DNA-binding protein 43 (TDP-43) aggregation that occurs in 97% of ALS cases. Here we examine spatial relationships between microglial activation and TDP-43 pathology in brain tissue from people with ALS and from a TDP-43-driven ALS mouse model. Post-mortem human brain tissue from the Neurological Foundation Human Brain Bank was obtained from 10 control and 10 ALS cases in parallel with brain tissue from a bigenicNEFH-tTA/tetO-hTDP-43∆NLS (rNLS) mouse model of ALS at disease onset, early disease, and late disease stages. The spatiotemporal relationship between microglial activation and ALS pathology was determined by investigating microglial functional marker expression in brain regions with low and high TDP-43 burden at end-stage human disease: hippocampus and motor cortex, respectively. Sections were immunohistochemically labelled with a two-round multiplexed antibody panel against; microglial functional markers (L-ferritin, HLA-DR, CD74, CD68, and Iba1), a neuronal marker, an astrocyte marker, and pathological phosphorylated TDP-43 (pTDP-43). Single-cell levels of microglial functional markers were quantified using custom analysis pipelines and mapped to anatomical regions and ALS pathology. We identified a significant increase in microglial Iba1 and CD68 expression in the human ALS motor cortex, with microglial CD68 being significantly correlated with pTDP-43 pathology load. We also identified two subpopulations of microglia enriched in the ALS motor cortex that were defined by high L-ferritin expression. A similar pattern of microglial changes was observed in the rNLS mouse, with an increase first in CD68 and then in L-ferritin expression, with both occurring only after pTDP-43 inclusions were detectable. Our data strongly suggest that microglia are phagocytic at early-stage ALS but transition to a dysfunctional state at end-stage disease, and that these functional states are driven by pTDP-43 aggregation. Overall, these findings enhance our understanding of microglial phenotypes and function in ALS.
Big Data and precision agriculture: a novel spatio-temporal semantic IoT data management framework for improved interoperability
Authors: San Emeterio de la Parte Mario , Martínez-Ortega José-Fernán , Hernández Díaz Vicente , Martínez Néstor Lucas
Published: April 2023

Precision agriculture in the realm of the Internet of Things is characterized by the collection of data from multiple sensors deployed on the farm. These data present a spatial, temporal, and semantic characterization, which further complicates the performance in the management and implementation of models and repositories. In turn, the lack of standards is reflected in insufficient interoperability between management solutions and other non-native services in the framework. In this paper, an innovative system for spatio-temporal semantic data management is proposed. It includes a data query system that allows farmers and users to solve queries daily, as well as feed decision-making, monitoring, and task automation solutions. In the proposal, a solution is provided to ensure service interoperability and is validated against two European smart farming platforms, namely AFarCloud and DEMETER. For the evaluation and validation of the proposed framework, a neural network is implemented, fed through STSDaMaS for training and validation, to provide accurate forecasts for the harvest and baling of forage legume crops for livestock feeding. As a result of the evaluation for the training and execution of neural networks, high performance on complex spatio-temporal semantic queries is exposed. The paper concludes with a distributed framework for managing complex spatio-temporal semantic data by offering service interoperability through data integration to external agricultural data models.

Graphical Abstract
Governance and sustainability of distributed continuum systems: a big data approach
Authors: Donta Praveen Kumar , Sedlak Boris , Casamayor Pujol Victor , Dustdar Schahram
Published: April 2023

Distributed computing continuum systems (DCCS) make use of a vast number of computing devices to process data generated by edge devices such as the Internet of Things and sensor nodes. Besides performing computations, these devices also produce data including, for example, event logs, configuration files, network management information. When these data are analyzed, we can learn more about the devices, such as their capabilities, processing efficiency, resource usage, and failure prediction. However, these data are available in different forms and have different attributes due to the highly heterogeneous nature of DCCS. The diversity of data poses various challenges which we discuss by relating them to big data, so that we can utilize the advantages of big data analytical tools. We enumerate several existing tools that can perform the monitoring task and also summarize their characteristics. Further, we provide a general governance and sustainable architecture for DCCS, which reflects the human body’s self-healing model. The proposed model has three stages: first, it analyzes system data to acquire knowledge; second, it can leverage the knowledge to monitor and predict future conditions; and third, it takes further actions to autonomously solve any issue or to alert administrators. Thus, the DCCS model is designed to minimize the system’s downtime while optimizing resource usage. A small set of data is used to illustrate the monitoring and prediction of the performance of a system through Bayesian network structure learning. Finally, we discuss the limitations of the governance and sustainability model, and we provide possible solutions to overcome them and make the system more efficient.
Review: A Roadmap to Use Nonstructured Data to Discover Multitarget Cancer Therapies
Authors: Scoarta Silvia , Küçükosmanoglu Asli , Bindt Felix , Pouwer Marianne , Westerman Bart A.
Published: April 2023

Therapy resistance to single agents has led to the realization that combination therapies could become the cornerstone of cancer treatment. To operationalize the selection of effective and safe multitarget therapies, we propose to integrate chemical and preclinical therapeutic information with clinical efficacy and toxicity data, allowing a new perspective on the drug target landscape. To assess the feasibility of this approach, we evaluated the publicly available chemical, preclinical, and clinical therapeutic data, and we addressed some potential limitations while integrating the data. First, by mapping available structured data from the main biomedical resources, we noticed that there is only a 1.7% overlap between drugs in chemical, preclinical, or clinical databases. Especially, the limited amount of structured data in the clinical domain hinders linking drugs to clinical aspects such as efficacy and side effects. Second, to overcome the abovementioned knowledge gap between the chemical, preclinical, and clinical domain, we suggest information extraction from scientific literature and other unstructured resources through natural language processing models, where BioBERT and PubMedBERT are the current state-of-the-art approaches. Finally, we propose that knowledge graphs can be used to link structured data, scientific literature, and electronic health records, to come to meaningful interpretations. Together, we expect this richer knowledge will lower barriers toward clinical application of personalized combination therapies with high efficacy and limited adverse events.
Transitions in development – an interview with Bhavana Muralidharan
Authors: Routledge Daniel
Published: April 2023

Bhavana Muralidharan is an Assistant Professor at the Institute for Stem Cell Science and Regenerative Medicine (inStem), where her research focuses on chromatin-mediated regulation of neurodevelopment and neuropsychiatric disorders, and the development of cerebral organoids for modelling these disorders in vitro. We caught up with Bhavana over Zoom to discuss her research, the recent EMBO organoid meeting hosted at inStem and her creative performances outside of the lab.
Association of Laparoscopic Surgery with Improved Perioperative and Survival Outcomes in Patients with Resectable Intrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis from Propensity-Score Matched Studies
Authors: Aliseda Daniel , Sapisochin Gonzalo , Martí-Cruchaga Pablo , Zozaya Gabriel , Blanco Nuria , Goh Brian K. P. , Rotellar Fernando
Published: April 2023

Background

Recent studies have associated laparoscopic surgery with better overall survival (OS) in patients with hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM). The potential benefits of laparoscopic liver resection (LLR) over open liver resection (OLR) have not been demonstrated in patients with intrahepatic cholangiocarcinoma (iCC).

Methods

A systematic review of the PubMed, EMBASE, and Web of Science databases was performed to search studies comparing OS and perioperative outcome for patients with resectable iCC. Propensity-score matched (PSM) studies published from database inception to May 1, 2022 were eligible. A frequentist, patient-level, one-stage meta-analysis was performed to analyze the differences in OS between LLR and OLR. Second, intraoperative, postoperative, and oncological outcomes were compared between the two approaches by using a random-effects DerSimonian-Laird model.

Results

Six PSM studies involving data from 1.042 patients (530 OLR vs. 512 LLR) were included. LLR in patients with resectable iCC was found to significantly decrease the hazard of death (stratified hazard ratio [HR]: 0.795 [95% confidence interval [CI]: 0.638–0.992]) compared with OLR. Moreover, LLR appears to be significantly associated with a decrease in intraoperative bleeding (− 161.47 ml [95% CI − 237.26 to − 85.69 ml]) and transfusion (OR = 0.41 [95% CI 0.26–0.69]), as well as with a shorter hospital stay (− 3.16 days [95% CI − 4.98 to − 1.34]) and a lower rate of major (Clavien-Dindo ≥III) complications (OR = 0.60 [95% CI 0.39–0.93]).

Conclusions

This large meta-analysis of PSM studies shows that LLR in patients with resectable iCC is associated with improved perioperative outcomes and, being conservative, yields similar OS outcomes compared with OLR.
Go with the Politician
Authors: Nian Yongwei , Wang Chunyang
Published: April 2023

Chinese local leaders are frequently moved across prefectures. By combining local leader rotation data and comprehensive firm land parcel purchase data across prefectures from 2006 to 2016, this paper examines how firm–politician connections affect resource allocation and finds that a firm headquartered in a leader’s previous work prefecture purchases three times more land parcels in that leader’s new governing prefecture than the prefecture-year mean, at half the unit prices. Identification is from within-firm-year variation in various prefectures through exogenous politician rotation. Land usage efficiency is lower for these follower firms’ land parcels. Land allocation distortion is also economically sizable. (JEL D22, D72, O17, O18, P25, P26)
Ο ανθρώπινος εγκέφαλος και ο νους μέσα από κείμενα
Authors: Μανδράκης Παναγιώτης
Published: April 2023

Βασικό ρόλο στα πρώτα στάδια της προσπάθειας για την κατανόηση του εγκεφάλου έπαιξε η κρανιοανάτρηση. Μόνο με το άνοιγμα του κρανίου είχαν οι μελετητές άμεση αντίληψη για το τι υπάρχει εντός του κρανίου και μια πρώτη γνώση για το τι γίνεται μέσα σ’ αυτό. Και ενώ σε κάποιες εποχές, κοινωνίες όπως η Κάτω Ιταλία τον 6ο αιώνα π.Χ έδωσαν μεγάλη ώθηση στη γνώση αυτή μέσα από τις ανατομές στο ανθρώπινο σώμα, πολλές κοινωνίες απαγόρευαν τις παραπάνω ανατομές και κρανιοανατρήσεις. Η απαγόρευση των κρανιοανατρήσεων συντέλεσε για μεγάλα χρονικά διαστήματα στη στασιμότητα της σχετικής με τον εγκέφαλο γνώσης, το πρωτεύον αυτό κέντρο ρύθμισης και συντονισμού των δραστηριοτήτων του οργανισμού, δεδομένου ότι αποτελεί την έδρα της συνείδησης, της σκέψης, της μνήμης, της λογικής, της κρίσης και του συναισθήματος. Αλλά και για την εξέταση του ανθρώπινου νου, συγκεντρώθηκαν τα σχετικά κείμενα και ταξινομήθηκαν χρονικά, έτσι ώστε να γίνει αντιληπτή η πορεία που ακολούθησε η προσπάθεια του ανθρώπου να κατανοήσει την έννοια του νου και ποια είναι η σχέση του με τον εγκέφαλο. Το να κουνήσει λ.χ. κάποιος το χέρι του είναι μια πράξη του νου. Η αθέλητη όμως κίνηση του χεριού που μπορεί να γίνει με το πάτημα του αντίστοιχου νεύρου μέσα σε ένα ανοιχτό κρανίο, είναι πράξη που πυροδοτεί ο εγκέφαλος. Ο νους είναι ο χρήστης του εγκεφάλου. Δημιουργεί τα πάντα στον εγκέφαλο, αφού τον αναδιαμορφώνει κάθε στιγμή και εντέλλεται τη δημιουργία των χημικών του ουσιών. Άποψη πολλών αρχαίων Ελλήνων φιλοσόφων ήταν ότι ο νους, εκτός από τη βασική του σημασία η οποία ισοδυναμεί με την ανώτερη πνευματική δύναμη της γνώσης, ήταν και η λογική αρχή που διέπει ολόκληρο το σύμπαν. Έτσι, οι αρχαίοι Έλληνες φιλόσοφοι συνέδεαν το νου με την ψυχή, με το Θεό και με το σύμπαν.Από την αναζήτησή στις αρχαιότερες αλλά και στις νεότερες διασωθείσες μαρτυρίες σχετικά με τον εγκέφαλο και τον νου, προκύπτει ότι τα πρόσφατα πνευματικά και τεχνολογικά επιτεύγματά του ανθρώπου στις επιστήμες του εγκεφάλου είναι εξελικτικά και δεν προέκυψαν με κάποιο μαγικό τρόπο. Πολλές από τις εξελίξεις στις νευροεπιστήμες μπορούν να ανιχνευτούν σε ιδέες και αντιλήψεις των προκατόχων τους, όπως παλαιότερων συγγραφέων που διέπρεψαν κατά τους προ Χριστού αιώνες, ενώ και στα χρόνια του Διαφωτισμού παρατηρείται μια μεταστροφή στη μελέτη των αρχαίων κειμένων, που οδηγεί στη διατύπωση διαφορετικών συμπερασμάτων σχετικών με τη λειτουργία του εγκεφάλου. Ωστόσο, τα πιο σημαντικά βήματα της νευροεπιστήμης πραγματοποιήθηκαν μετά το 1950 λόγω του καθοριστικού ρόλου των υπολογιστών και της ψηφιακής τεχνολογίας. Το γεγονός ότι στις αρχές του 21ο αιώνα κυριαρχούν οι Νευροεπιστήμες στην επιστημονική έρευνα επιβεβαιώνεται περίτρανα τόσο από την εντυπωσιακή αύξηση –ποσοτική και ποιοτική- των ερευνητικών προγραμμάτων τα οποία στοχεύουν στην αποκάλυψη των επτασφράγιστων μυστικών του εγκεφάλου και του νου, όσο και από τα ασυνήθιστα μεγάλα ποσά που επενδύονται από δημόσιους και ιδιωτικούς φορείς για τις έρευνες αυτές. Η μελέτη του εγκεφάλου και του νου λοιπόν και από ιστορικοφιλοσοφική άποψη είναι επιβεβλημένη.
Inauguration of Technical Annals e-publishing
Authors: Stasinos George Ν.
Published: April 2023

With particular joy, respect and commitment to the history of TEE, to the future of the scientific role of the Chamber and to the work of Greek Engineers as a whole, the Technical Chamber of Greece is proceeding with the publication of an international scientific journal. After several years without regular scientific publications, due to the special economic situation of the country, but having as a source of our history the TECHNICAL ANNALS, published by the TEE for decades, we undertake this role again to give another scientific podium to the Engineering community.
Historic building and green energy. Strategies to make supply from renewable sources compatible with conservation
Authors: Trovò Francesco
Published: April 2023

The challenges of today are largely summarized in the United Nations 2030 Agenda. Buildings are also part of the 17 sustainability goals in several respects, one of them being the role of reducing climate-altering emissions, reducing waste, assessing the life cycle of materials, limiting heat loss and introducing renewable energy sources. In particular, the contribution deals with how to ensure the supply of energy from renewable sources for cultural assets and buildings that are part of historic centers. In these cases it can be very difficult to achieve both the objective of protecting the monument or landscape as well as that of installing or connecting the building or urban or rural settlement to renewable energy sources. Through some European and Italian examples in particular, where about 8 million buildings were constructed before 1945, about 25% of the total, virtuous ways will be presented that make it possible to achieve both objectives simultaneously. The regulations that favor this dual objective will also be highlighted, such as the one of the Veneto Region on so-called energy communities and the national one that allows the deferral of energy production from one place of cultural interest to another that has none, without serious costs for the final beneficiary and safeguarding the cultural asset.