bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of type 2 diabetes on complications after primary breast cancer surgery: Danish population-based cohort study
Authors: Kjærgaard Kasper , Wheler Jannik , Dihge Looket , Christiansen Peer , Borgquist Signe , Cronin-Fenton Deirdre
Published: March 2024

Background

Knowledge is sparse on the impact of type 2 diabetes (T2D) on surgical outcomes after breast cancer surgery. This study investigated the association between T2D and risk of complications after primary breast cancer surgery, and evaluated the biological interaction between T2D and co-morbidities.

Methods

Using the Danish Breast Cancer Group clinical database, a cohort of all Danish women diagnosed with early-stage breast cancer during 1996–2022 was created. All patients underwent mastectomy or breast-conserving surgery. Information on prevalent T2D was collected from Danish medical and prescription registries. Surgical complications were defined as hospital diagnoses for medical or surgical complications developing within 30 days after primary breast cancer surgery. The 30-day cumulative incidence proportion of complications was calculated, and Cox regression was used to estimate HRs. Interaction contrasts were computed to determine the additive interaction between T2D and co-morbidities on the incidence rate of complications.

Results

Among 98 589 women with breast cancer, 6332 (6.4%) had T2D at breast cancer surgery. Overall, 1038 (16.4%) and 9861 (10.7%) women with and without T2D developed surgical complications, yielding cumulative incidence proportions of 16 (95% c.i. 15 to 17) and 11 (10 to 11)% respectively, and a HR of 1.43 (95% c.i. 1.34 to 1.53). The incidence rate of surgical complications explained by the interaction of T2D with moderate and severe co-morbidity was 21 and 42%, respectively.

Conclusion

Women with breast cancer and T2D had a higher risk of complications after primary breast cancer surgery than those without T2D. A synergistic effect of T2D and co-morbidity on surgical complications can explain this association.
Association of abnormal explicit sense of agency with cerebellar impairment in myoclonus-dystonia
Authors: Tarrano Clément , Galléa Cécile , Delorme Cécile , McGovern Eavan M , Atkinson-Clement Cyril , Barnham Isaac Jarratt , Brochard Vanessa , Thobois Stéphane , Tranchant Christine , Grabli David , Degos Bertrand , Corvol Jean Christophe , Pedespan Jean-Michel , Krystkowiak Pierre , Houeto Jean-Luc , Degardin Adrian , Defebvre Luc , Valabrègue Romain , Beranger Benoit , Apartis Emmanuelle , Vidailhet Marie , Roze Emmanuel , Worbe Yulia
Published: March 2024

Non-motor aspects in dystonia are now well recognized. The sense of agency, which refers to the experience of controlling one's own actions, has been scarcely studied in dystonia, even though its disturbances can contribute to movement disorders. Among various brain structures, the cerebral cortex, the cerebellum, and the basal ganglia are involved in shaping the sense of agency. In myoclonus dystonia, resulting from a dysfunction of the motor network, an altered sense of agency may contribute to the clinical phenotype of the condition. In this study, we compared the explicit and implicit sense of agency in patients with myoclonus dystonia caused by a pathogenic variant of SGCE (DYT-SGCE) and control participants. We utilized behavioural tasks to assess the sense of agency and performed neuroimaging analyses, including structural, resting-state functional connectivity, and dynamic causal modelling, to explore the relevant brain regions involved in the sense of agency. Additionally, we examined the relationship between behavioural performance, symptom severity, and neuroimaging findings. We compared 19 patients with DYT-SGCE and 24 healthy volunteers. Our findings revealed that patients with myoclonus-dystonia exhibited a specific impairment in explicit sense of agency, particularly when implicit motor learning was involved. However, their implicit sense of agency remained intact. These patients also displayed grey-matter abnormalities in the motor cerebellum, as well as increased functional connectivity between the cerebellum and pre-supplementary motor area. Dynamic causal modelling analysis further identified reduced inhibitory effects of the cerebellum on the pre-supplementary motor area, decreased excitatory effects of the pre-supplementary motor area on the cerebellum, and increased self-inhibition within the pre-supplementary motor area. Importantly, both cerebellar grey-matter alterations and functional connectivity abnormalities between the cerebellum and pre-supplementary motor area were found to correlate with explicit sense of agency impairment. Increased self-inhibition within the pre-supplementary motor area was associated with less severe myoclonus symptoms. These findings highlight the disruption of higher-level cognitive processes in patients with myoclonus-dystonia, further expanding the spectrum of neurological and psychiatric dysfunction already identified in this disorder.
Molecular diversity in isocitrate dehydrogenase-wild-type glioblastoma
Authors: Fares Jawad , Wan Yizhou , Mair Richard , Price Stephen J
Published: March 2024

In the dynamic landscape of glioblastoma, the 2021 World Health Organization Classification of Central Nervous System tumours endeavoured to establish biological homogeneity, yet isocitrate dehydrogenase-wild-type (IDH-wt) glioblastoma persists as a tapestry of clinical and molecular diversity. Intertumoural heterogeneity in IDH-wt glioblastoma presents a formidable challenge in treatment strategies. Recent strides in genetics and molecular biology have enhanced diagnostic precision, revealing distinct subtypes and invasive patterns that influence survival in patients with IDH-wt glioblastoma. Genetic and molecular biomarkers, such as the overexpression of neurofibromin 1, phosphatase and tensin homolog and/or cyclin-dependent kinase inhibitor 2A, along with specific immune cell abundance and neurotransmitters, correlate with favourable outcomes. Conversely, increased expression of epidermal growth factor receptor tyrosine kinase, platelet-derived growth factor receptor alpha and/or vascular endothelial growth factor receptor, coupled with the prevalence of glioma stem cells, tumour-associated myeloid cells, regulatory T cells and exhausted effector cells, signifies an unfavourable prognosis. The methylation status of O6-methylguanine–DNA methyltransferase and the influence of microenvironmental factors and neurotransmitters further shape treatment responses. Understanding intertumoural heterogeneity is complemented by insights into intratumoural dynamics and cellular interactions within the tumour microenvironment. Glioma stem cells and immune cell composition significantly impact progression and outcomes, emphasizing the need for personalized therapies targeting pro-tumoural signalling pathways and resistance mechanisms. A successful glioblastoma management demands biomarker identification, combination therapies and a nuanced approach considering intratumoural variability. These advancements herald a transformative era in glioblastoma comprehension and treatment.
Drug-induced myocarditis precipitated by amlodipine overdose: a case report
Authors: Skaria Maria , Hoey Edward , Watkin Richard , Skaria Binoy
Published: March 2024

Background

Amlodipine is the most commonly prescribed calcium channel blocker (CCB), used in the treatment of a variety of cardiovascular conditions. Calcium channel blockers remain a well-established cause of cardiovascular drug overdose. We present the case of an intentional overdose with 250 mg of amlodipine resulting in acute left ventricular dysfunction and myocarditis.

Case summary

A 46-year-old man with no significant past medical history presented to the emergency department 8 h after intentionally ingesting 250 mg of amlodipine. Although initially asymptomatic with unremarkable physical examination, the patient developed progressively worsening dyspnoea over the next 2 days. Subsequent findings from chest X-ray, electrocardiogram, echocardiogram, and cardiac magnetic resonance imaging (MRI) were consistent with a diffuse myocarditis process with severe left ventricular systolic dysfunction. The patient was managed with diuretics and discharged once stable.

Discussion

Our case highlights myocarditis as a potential complication of CCB overdose. Amlodipine is the most commonly prescribed CCB and is associated with cardiac toxicity at high doses. The long duration of action and high volume of distribution of amlodipine further increase the risk of morbidity and mortality from overdose. Known cardiac complications of amlodipine overdose include bradycardia, myocardial depression, and pulmonary oedema secondary to heart failure; however, diffuse myocarditis is a complication that has not previously been described in the literature. The mechanism of development of this complication remains unclear.
Business creation during COVID-19
Authors: Bahaj Saleem , Piton Sophie , Savagar Anthony
Published: March 2024

Using UK data, we present greater empirical detail on the puzzling firm dynamics that emerged during coronavirus disease 2019 (COVID-19). We show that firm entry increased during the pandemic across several countries, and this contrasts with typical recessions where firm entry declines. Additionally, the rise in firm entry is driven by individual entrepreneurs creating companies for the first time, particularly in online retail. We find evidence that firm creation responded significantly to declines in retail footfall and that firms created during the pandemic are more likely to exit and less likely to post jobs. Overall, this implies that despite surging firm creation during the pandemic, the overall employment effect is limited. Finally, we find that the primary contributor to limited employment creation is the shift in ownership composition of new entrants during COVID.
Automated isochronal late activation mapping for substrate characterization in patients with repaired tetralogy of Fallot
Authors: Arana-Rueda Eduardo , Acosta Juan , Frutos-López Manuel , Sánchez-Brotons Juan-Antonio , González de la Portilla-Concha Carmen , Gallego Pastora , Pedrote Alonso
Published: March 2024

Aims

Slow conduction (SC) anatomical isthmuses (AIs) are the dominant substrate for monomorphic ventricular tachycardia (VT) in patients with repaired tetralogy of Fallot (rTF). This study aimed to evaluate the utility of automated propagational analysis for the identification of SC-AI in patients with rTF.

Methods and results

Consecutive rTF patients undergoing VT substrate characterization were included. Automated isochronal late activation maps (ILAM) were obtained with multielectrode HD Grid Catheter. Identified deceleration zones (DZs) were compared with both SC-AI defined by conduction velocity (CV) (<0.5 m/s) and isthmuses of induced VT for mechanistic correlation. Fourteen patients were included (age 48; p25–75 35–52 years; 57% male), 2 with spontaneous VT and 12 for risk stratification. Nine VTs were inducible in seven patients. Procedure time was 140 (p25–75 133–180) min and mapping time 29.5 (p25–75 20–37.7) min, using a median of 2167 points. All the patients had at least one AI by substrate mapping, identifying a total of 27 (11 SC-AIs). Isochronal late activation maps detected 10 DZs mostly in the AI between ventricular septal defect and pulmonary valve (80%). Five patients had no DZs. A significant negative correlation between number of isochrones/cm and CV was observed (rho −0.87; P < 0.001). Deceleration zones correctly identified SC-AI (90% sensitivity; 100% specificity; 0.94 accuracy) and was related to VT inducibility (P = 0.006). Deceleration zones co-localized to the critical isthmus of induced VTs in 88% of cases. No complications were observed.

Conclusion

Deceleration zones displayed by ILAM during sinus rhythm accurately identify SC-AIs in rTF patients allowing a safe and short-time VT substrate characterization procedure.
Validation of a novel smartphone-based photoplethysmographic method for ambulatory heart rhythm diagnostics: the SMARTBEATS study
Authors: Fernstad Jonatan , Svennberg Emma , Åberg Peter , Kemp Gudmundsdottir Katrin , Jansson Anders , Engdahl Johan
Published: March 2024

Aims

In the current guidelines, smartphone photoplethysmography (PPG) is not recommended for diagnosis of atrial fibrillation (AF), without a confirmatory electrocardiogram (ECG) recording. Previous validation studies have been performed under supervision in healthcare settings, with limited generalizability of the results. We aim to investigate the diagnostic performance of a smartphone-PPG method in a real-world setting, with ambulatory unsupervised smartphone-PPG recordings, compared with simultaneous ECG recordings and including patients with atrial flutter (AFL).

Methods and results

Unselected patients undergoing direct current cardioversion for treatment of AF or AFL were asked to perform 1-min heart rhythm recordings post-treatment, at least twice daily for 30 days at home, using an iPhone 7 smartphone running the CORAI Heart Monitor PPG application simultaneously with a single-lead ECG recording (KardiaMobile). Photoplethysmography and ECG recordings were read independently by two experienced readers. In total, 280 patients recorded 18 005 simultaneous PPG and ECG recordings. Sufficient quality for diagnosis was seen in 96.9% (PPG) vs. 95.1% (ECG) of the recordings (P < 0.001). Manual reading of the PPG recordings, compared with manually interpreted ECG recordings, had a sensitivity, specificity, and overall accuracy of 97.7%, 99.4%, and 98.9% with AFL recordings included and 99.0%, 99.7%, and 99.5%, respectively, with AFL recordings excluded.

Conclusion

A novel smartphone-PPG method can be used by patients unsupervised at home to achieve accurate heart rhythm diagnostics of AF and AFL with very high sensitivity and specificity. This smartphone-PPG device can be used as an independent heart rhythm diagnostic device following cardioversion, without the requirement of confirmation with ECG.
Salmonella enterica serovar Typhimurium ST313 sublineage 2.2 has emerged in Malawi with a characteristic gene expression signature and a fitness advantage
Authors: Kumwenda Benjamin , Canals Rocío , Predeus Alexander V , Zhu Xiaojun , Kröger Carsten , Pulford Caisey , Wenner Nicolas , Lora Lizeth Lacharme , Li Yan , Owen Siân V , Everett Dean , Hokamp Karsten , Heyderman Robert S , Ashton Philip M , Gordon Melita A , Msefula Chisomo L , Hinton Jay C D
Published: March 2024

Invasive non-typhoidal Salmonella (iNTS) disease is a serious bloodstream infection that targets immune-compromised individuals, and causes significant mortality in sub-Saharan Africa. Salmonella enterica serovar Typhimurium ST313 causes the majority of iNTS in Malawi. We performed an intensive comparative genomic analysis of 608 S. Typhimurium ST313 isolates dating between 1996 and 2018 from Blantyre, Malawi. We discovered that following the arrival of the well-characterized S. Typhimurium ST313 lineage 2 in 1999, two multidrug-resistant variants emerged in Malawi in 2006 and 2008, designated sublineages 2.2 and 2.3, respectively. The majority of S. Typhimurium isolates from human bloodstream infections in Malawi now belong to sublineages 2.2 or 2.3. To understand the emergence of the prevalent ST313 sublineage 2.2, we studied two representative strains, D23580 (lineage 2) and D37712 (sublineage 2.2). The chromosome of ST313 lineage 2 and sublineage 2.2 only differed by 29 SNPs/small indels and a 3 kb deletion of a Gifsy-2 prophage region including the sseI pseudogene. Lineage 2 and sublineage 2.2 had distinctive plasmid profiles. The transcriptome was investigated in 15 infection-relevant in vitro conditions and within macrophages. During growth in physiological conditions that do not usually trigger S. Typhimurium SPI2 gene expression, the SPI2 genes of D37712 were transcriptionally active. We identified down-regulation of flagellar genes in D37712 compared with D23580. Following phenotypic confirmation of transcriptomic differences, we discovered that sublineage 2.2 had increased fitness compared with lineage 2 during mixed growth in minimal media. We speculate that this competitive advantage is contributing to the emergence of sublineage 2.2 in Malawi.
Reliability of Noninvasive Sonic Tomography for Detection and Quantification of Internal Defects in Yoshino Cherry
Authors: Lee Gwanggyu , Son Jiwon
Published: March 2024

Preventive maintenance through monitoring and early detection is important for trees that are structurally weak due to internal decay. Once internal decay has occurred, recovery of lost strength is irreversible. The decaying tree becomes vulnerable to external impacts, which may lead to breakage or windthrow. The Yoshino cherry (Cerasus×yedoensis (Matsum.) “Somei-yoshino”) accounts for a high proportion of landscape trees in Asia. Testing the reliability of noninvasive sonic tomography (SoT) to estimate internal defects could facilitate structural stability evaluation and proactive preventive management. We performed noninvasive SoT and invasive resistance microdrilling to detect and quantify internal defects in old and large Yoshino cherry trees. Generally, SoT reflected the areas and location of severe structural defects, showing a correlation with the resistance microdrilling results (R² = 0.542, p < .001). However, when cracks were present in disks, the SoT overestimated defects and errors mainly observed in the transition zone (green). Based on these findings, when evaluating the SoT, careful decisions are needed to distinguish between actual defects and broad sonic shadows. Furthermore, additional evidence from drilling resistance is required to differentiate between incipient decay and cracks. The results of this study provide valuable insights for enhancing the interpretation of sonic tomograms.

Study Implications: We suggest defect boundaries in sonic tomograms should be redefined to improve the accuracy of interpretation for any new species being studied. Careful drilling resistance measurements should be taken, especially in transition zones (green areas in tomogram) and incipient decay zone (light brown areas). Noninvasive sonic tomograms only reflect acoustic properties of the tested cross-section of a tree and cannot be considered an actual representation of the internal conditions until the readings are calibrated to destructive sampling results.
Chromosome-level genome assembly of the European green woodpecker Picus viridis
Authors: Forest Thomas , Achaz Guillaume , Marbouty Martial , Bignaud Amaury , Thierry Agnès , Koszul Romain , Milhes Marine , Lledo Joanna , Pons Jean-Marc , Fuchs Jérôme
Published: March 2024

The European green woodpecker, Picus viridis, is a widely distributed species found in the Western Palearctic region. Here, we assembled a highly contiguous genome assembly for this species using a combination of short- and long-read sequencing and scaffolded with chromatin conformation capture (Hi-C). The final genome assembly was 1.28 Gb and features a scaffold N50 of 37 Mb and a scaffold L50 of 39.165 Mb. The assembly incorporates 89.4% of the genes identified in birds in OrthoDB. Gene and repetitive content annotation on the assembly detected 15,805 genes and a ∼30.1% occurrence of repetitive elements, respectively. Analysis of synteny demonstrates the fragmented nature of the P. viridis genome when compared to the chicken (Gallus gallus). The assembly and annotations produced in this study will certainly help for further research into the genomics of P. viridis and the comparative evolution of woodpeckers. Five historical and seven contemporary samples have been resequenced and may give insights on the population history of this species.
Separation of fast and slow shear waves and prediction of fracture parameters based on non-orthogonal assumptions
Authors: Luo Chuan , Yang Yuyong , Zhou Huailai , Wang Yuanjun
Published: March 2024

Natural fractures play a significant role in oil and gas reservoirs. Accurate predictions of fracture parameters are vital in reservoir prediction and oil and gas development. The birefringent phenomenon of shear waves in fractured media makes shear wave splitting (SWS) analysis an important tool in formulating fracture predictions. The traditional SWS analysis method is based on an orthogonal assumption of fast and slow shear waves. However, in an orthotropic medium composed of a background vertical transversely isotropic medium and a set of vertical fractures, fast and slow shear waves are not necessarily orthogonal. This causes the traditional SWS analysis method to fail. To solve this problem, we proposed an SWS analysis algorithm with a non-orthogonal assumption of fast and slow shear waves in this study. First, we introduced a parameter (difference angle) to characterize the angle between slow shear waves and the normal polarization directions of the fast shear waves. Subsequently, based on the traditional two-parameter scanning algorithm, a parameter was added to facilitate three-parameter scanning. In addition, we derived an expression for the two-parameter scanning objective function using the non-orthogonal assumption. Two-parameter scanning can accurately extract fast and slow wave time delay data, but it cannot determine an accurate fast shear wave polarization direction. Therefore, we optimized the three-parameter scanning algorithm as follows: first, we used two-parameter scanning to obtain the fast and slow wave time delays and then performed further scanning to determine the polarization direction of the fast shear wave and difference angle. The optimization algorithm significantly improved the computational efficiency. Subsequently, we tested the accuracy of this method using synthetic single-trace and three-component vertical seismic profile data. We demonstrated the implementation process of the three-parameter scanning method using actual data, separated fast and slow shear waves, and predicted fracture parameters. The final fracture parameters were verified.
Prospective Evaluation of Serum Free Thiols in Inflammatory Bowel Disease: A Candidate to Replace C-Reactive Protein for Disease Activity Assessment?
Authors: Bohra Anuj , Batt Nicholas , Dutt Krishneel , Sluka Pavel , Niewiadomski Olga , Vasudevan Abhinav , Van Langenberg Daniel R
Published: March 2024

Background

Serum free thiols (SFTs) reflecting oxidative stress appear to correlate with inflammatory bowel disease (IBD) activity. We aimed to evaluate the performance of SFTs concentrations vs endoscopic and histological activity, compare SFTs with established biomarkers, and identify clinical and laboratory parameters independently associated with SFT levels in IBD patients.

Methods

Patients with confirmed IBD undergoing routine ileocolonoscopy for activity assessment were prospectively recruited, with serum samples obtained concurrently for SFTs and routine bloods, plus fecal calprotectin and immunochemical tests were collected ±30 days from ileocolonoscopy. Endoscopic activity was assessed via established indices and histological activity graded as inactive/mild/moderate. Receiver-operating characteristic curve analyses were utilized to assess performance of SFTs vs endoscopic activity, and multiple regression analysis was used to identify factors associated with SFT levels.

Results

A total of 141 (80 Crohn’s disease, 61 ulcerative colitis) patients were recruited. Median SFTs were significantly lower in moderate vs inactive/mild endoscopic activity (309 µM vs 433/471 µM, respectively; P < .01). There was no significant difference in median SFTs across inactive/mild/moderate histological activity. SFTs achieved higher sensitivity than C-reactive protein in predicting moderate, endoscopically active disease (89% vs 78%; area under the curve, 0.80 each) yet was outperformed by fecal calprotectin (100%; area under the curve, 0.93). Advancing age and increasing albumin levels were independently associated with SFT levels, and thus are possible confounders.

Conclusions

This prospective study has demonstrated the potential of SFTs as a serum biomarker in IBD. It was more sensitive than C-reactive protein, yet less sensitive than fecal biomarkers for prediction of endoscopically active IBD.
Eradication of Staphylococcus aureus in Implant-Associated Osteomyelitis by an Injectable In Situ-Forming Depot Antibiotics Delivery System
Authors: Fuglsang-Madsen Albert Juan , Henriksen Nicole Lind , Chávez Elizabeth Serrano , Kvich Lasse Andersson , Birch Julie Knippel Melsted , Hartmann Katrine Top , Eriksen Thomas , Bjarnsholt Thomas , Gottlieb Hans , Andresen Thomas Lars , Jensen Louise Kruse , Henriksen Jonas Rosager , Hansen Anders Elias
Published: March 2024

Background

Bone infections with Staphylococcus aureus are notoriously difficult to treat and have high recurrence rates. Local antibiotic delivery systems hold the potential to achieve high in situ antibiotic concentrations, which are otherwise challenging to achieve via systemic administration. Existing solutions have been shown to confer suboptimal drug release and distribution. Here we present and evaluate an injectable in situ-forming depot system termed CarboCell. The CarboCell technology provides sustained and tuneable release of local high-dose antibiotics.

Methods

CarboCell formulations of levofloxacin or clindamycin with or without antimicrobial adjuvants cis-2-decenoic acid or cis-11-methyl-2-dodecenoic acid were tested in experimental rodent and porcine implant-associated osteomyelitis models. In the porcine models, debridement and treatment with CarboCell-formulated antibiotics was carried out without systemic antibiotic administration. The bacterial burden was determined by quantitative bacteriology.

Results

CarboCell formulations eliminated S. aureus in infected implant rat models. In the translational implant-associated pig model, surgical debridement and injection of clindamycin-releasing CarboCell formulations resulted in pathogen-free bone tissues and implants in 9 of 12 and full eradication in 5 of 12 pigs.

Conclusions

Sustained release of antimicrobial agents mediated by the CarboCell technology demonstrated promising therapeutic efficacy in challenging translational models and may be beneficial in combination with the current standard of care.
CsiR-Mediated Signal Transduction Pathway in Response to Low Iron Conditions Promotes Escherichia coli K1 Invasion and Penetration of the Blood-Brain Barrier
Authors: Zheng Yangyang , Sun Hao , Wang Yanling , Jin Chen , Li Xiaoya , Pang Yu , Ge Qianwen , Wang Lei , Liu Bin
Published: March 2024

Escherichia coli K1 is the leading cause of neonatal gram-negative bacterial meningitis, but the pathogenesis of E coli K1 meningitis remains unclear. Blood-brain barrier (BBB) penetration is a crucial step in E coli meningitis development. Here, we uncovered the crucial role of CsiR, a GntR family regulator, in E coli K1 virulence. During infection, csiR expression was induced due to the derepression by Fur in the blood and human brain microvascular endothelial cells (HBMECs). CsiR positively regulated ilvB expression, which is associated with branched chain amino acid synthesis. Furthermore, we revealed that IlvB activated the FAK/PI3K pathway of HBMECs to induce actin cytoskeleton rearrangements, thereby promoting the bacterial invasion and penetration of the BBB. Overall, this study reveals a CsiR-mediated virulence regulation pathway in E coli K1, which may provide a useful target for the prevention or therapy of E coli meningitis.
Dryland microbiomes reveal community adaptations to desertification and climate change
Authors: Coleine Claudia , Delgado-Baquerizo Manuel , DiRuggiero Jocelyne , Guirado Emilio , Harfouche Antoine L , Perez-Fernandez Cesar , Singh Brajesh K , Selbmann Laura , Egidi Eleonora
Published: March 2024

Drylands account for 45% of the Earth’s land area, supporting ~40% of the global population. These regions support some of the most extreme environments on Earth, characterized by extreme temperatures, low and variable rainfall, and low soil fertility. In these biomes, microorganisms provide vital ecosystem services and have evolved distinctive adaptation strategies to endure and flourish in the extreme. However, dryland microbiomes and the ecosystem services they provide are under threat due to intensifying desertification and climate change. In this review, we provide a synthesis of our current understanding of microbial life in drylands, emphasizing the remarkable diversity and adaptations of these communities. We then discuss anthropogenic threats, including the influence of climate change on dryland microbiomes and outline current knowledge gaps. Finally, we propose research priorities to address those gaps and safeguard the sustainability of these fragile biomes.
Slightly acidic electrolyzed water significantly restrains the accumulation of the microalgae Pseudokirchneriella subcapitata in hydroponic systems
Authors: Wu Cuinan , Li Yuanyuan , Wu Xue , Bao Encai , Ye Lin , Cao Kai
Published: March 2024

Aims

This study explored the effects of slightly acidic electrolyzed water (SAEW) on algae to exploit technologies that effectively suppress algal growth in hydroponic systems and improve crop yield.

Methods and Results

The effects of SAEW on algal growth and the response mechanisms of algae to SAEW were investigated. Moreover, we studied whether the application of SAEW adversely affected tomato seedling growth. The results showed that SAEW significantly inhibited algal growth and destroyed the integrity of the algal cells. In addition, the intracellular oxidation−reduction system of algae was greatly influenced by SAEW. The H2O2, O2−, malondialdehyde (MDA), and reactive oxygen species (ROS) fluorescence signals were significantly induced by SAEW, and superoxide dismutase (SOD), peroxidase (POD), and glutathione reductase (GR) activities were greatly enhanced by a low SAEW concentration but significantly inhibited by SAEW with a high available chlorine concentration, which may contribute to heavy oxidative stress on algal growth and cell structure break down, eventually causing the death of algae and cell number decrease. We also found that regardless of the concentration of SAEW (from 10 to 40 mg L−1), there was no significant change in the germination index, length, or fresh weight of the hydroponic tomato seedlings.

Conclusions

Our findings demonstrate that SAEW can be used in hydroponic systems to restrain algae with no negative impact on tomato plants.
Estradiol induces bone osteolysis in triple–negative breast cancer via its membrane–associated receptor ERα36
Authors: Cohen D Joshua , Dennis Cydney D , Deng Jingyao , Boyan Barbara D , Schwartz Zvi
Published: March 2024

Triple–negative breast cancer (TNBC) is thought to be an estradiol–independent, hormone therapy–resistant cancer because of lack of estrogen receptor alpha 66 (ERα66). We identified a membrane–bound splice variant, ERα36, in TNBC cells that responds to estrogen (E2) and may contribute to bone osteolysis. We demonstrated that the MDA-MB-231 TNBC cell line, which expresses ERα36 similarly to MCF7 cells, is responsive to E2, forming osteolytic tumors in vivo. MDA-MB-231 cells activate osteoclasts in a paracrine manner. Conditioned media (CM) from MDA-MB-231 cells treated with bovine serum albumin–bound E2 (E2-BSA) increased activation of human osteoclast precursor cells; this was blocked by addition of anti–ERα36 antibody to the MDA-MB-231 cultures. Osteoclast activation and bone resorption genes were elevated in RAW 264.7 murine macrophages following treatment with E2-BSA–stimulated MDA-MB-231 CM. E2 and E2-BSA increased phospholipase C (PLC) and protein kinase C (PKC) activity in MDA-MB-231 cells. To examine the role of ERα36 signaling in bone osteolysis in TNBC, we used our bone–cancer interface mouse model in female athymic homozygous Foxn1nu mice. Mice with MDA-MB-231 tumors and treated with tamoxifen (TAM), E2, or TAM/E2 exhibited increased osteolysis, cortical bone breakdown, pathologic fracture, and tumor volume; the combined E2/TAM group also had reduced bone volume. These results suggest that E2 increased osteolytic lesions in TNBC through a membrane–mediated PLC/PKC pathway involving ERα36, which was enhanced by TAM, demonstrating the role of ERα36 and its membrane–associated signaling pathway in bone tumors. This work suggests that ERα36 may be a potential therapeutic target in patients with TNBC.
‘Learned Perception’ as a Form of ‘Religious Experience’: Jīva Gosvāmin’s Vaiduṣa-pratyakṣa
Authors: Uskokov Aleksandar
Published: March 2024

This article interprets the religious epistemology of the Caitanya Vaiṣṇava theologian Jīva Gosvāmin, specifically his division of perception in ‘learned’ and ‘ignorant’, to argue that ‘learned’ perception is supersensible cognitive experience shaped by learning and language. The article goes on to show that the contemporary scholarship on religious experience can learn an important lesson from Jīva’s epistemology, namely that the social construction of categories that shape religious experience need not involve ontological agnosticism with respect to the existence of objects presented in it.
A variable neighbourhood search for minimization of operation times through warehouse layout optimization
Authors: Díaz Jon , Rodriguez Haizea , Fajardo-Calderín Jenny , Angulo Ignacio , Onieva Enrique
Published: March 2024

For companies involved in the supply chain, proper warehousing management is crucial. Warehouse layout arrangement and operation play a critical role in a company’s ability to maintain and improve its competitiveness. Reducing costs and increasing efficiency are two of the most crucial warehousing goals. Deciding on the best warehouse layout is a remarkable optimization problem. This paper uses an optimization method to set bin allocations within an automated warehouse with particular characteristics. The warehouse’s initial layout and the automated platforms limit the search and define the time required to move goods within the warehouse. With the help of historical data and the definition of the time needed to move goods, a mathematical model of warehouse operation was created. An optimization procedure based on the well-known Variable Neighbourhood Search algorithm is defined and applied to the problem. Experimental results demonstrate increments in the efficiency of warehousing operations.
Field-Collected Ticks From Benton County, Arkansas, and Prevalence of Associated Pathogens
Authors: Panella Nicholas A , Nicholson William L , Komar Nicholas , Burkhalter Kristen L , Hughes Holly R , Theuret David P , Blocher Bessie H , Sexton Christopher , Connelly Roxanne , Rothfeldt Laura , Kenney Joan L
Published: March 2024

The recovery of a Haemaphysalis longicornis Neumann (Acari: Ixodidae) tick from a dog in Benton County, Arkansas, in 2018 triggered a significant environmental sampling effort in Hobbs State Park Conservation Area. The objective of the investigation was to assess the tick population density and diversity, as well as identify potential tick-borne pathogens that could pose a risk to public health. During a week-long sampling period in August of 2018, a total of 6,154 ticks were collected, with the majority identified as Amblyomma americanum (L), (Acari: Ixodidae) commonly known as the lone star tick. No H. longicornis ticks were found despite the initial detection of this species in the area. This discrepancy highlights the importance of continued monitoring efforts to understand the dynamics of tick populations and their movements. The investigation also focused on pathogen detection, with ticks being pooled by species, age, and sex before being processed with various bioassays. The results revealed the presence of several tick-borne pathogens, including agents associated with ehrlichiosis (n = 12), tularemia (n = 2), and Bourbon virus (BRBV) disease (n = 1), as well as nonpathogenic rickettsial and anaplasmosis organisms. These findings emphasize the importance of public health messaging to raise awareness of the risks associated with exposure to tick-borne pathogens. Prevention measures, such as wearing protective clothing, using insect repellent, and conducting regular tick checks, should be emphasized to reduce the risk of tick-borne diseases. Continued surveillance efforts and research are also essential to improve our understanding of tick-borne disease epidemiology and develop effective control strategies.
A Fictionalist Account of Open-Label Placebo
Authors: Hardman Doug
Published: March 2024

The placebo effect is now generally defined widely as an individual’s response to the psychosocial context of a clinical treatment, as distinct from the treatment’s characteristic physiological effects. Some researchers, however, argue that such a wide definition leads to confusion and misleading implications. In response, they propose a narrow definition restricted to the therapeutic effects of deliberate placebo treatments. Within the framework of modern medicine, such a scope currently leaves one viable placebo treatment paradigm: the non-deceptive and non-concealed administration of “placebo pills” or open-label placebo (OLP) treatment. In this paper, I consider how the placebo effect occurs in OLP. I argue that a traditional, belief-based account of OLP is paradoxical. Instead, I propose an account based on the non-doxastic attitude of pretence, understood within a fictionalist framework.
The Social Epistemology of Clinical Placebos
Authors: Rees Melissa
Published: March 2024

Many extant theories of placebo focus on their causal structure wherein placebo effects are those that originate from select features of the therapy (e.g., client expectations or “incidental” features like size and shape). Although such accounts can distinguish placebos from standard medical treatments, they cannot distinguish placebos from everyday occurrences, for example, when positive feedback improves our performance on a task. Providing a social-epistemological account of a treatment context can rule out such occurrences, and furthermore reveal a new way to distinguish clinical placebos from standard medical treatments.
The Altruism Requirement as Moral Fiction
Authors: Semrau Luke
Published: March 2024

It is widely agreed that living kidney donation is permitted but living kidney sales are not. Call this the Received View. One way to support the Received View is to appeal to a particular understanding of the conditions under which living kidney transplantation is permissible. It is often claimed that donors must act altruistically, without the expectation of payment and for the sake of another. Call this the Altruism Requirement. On the conventional interpretation, the Altruism Requirement is a moral fact. It states a legitimate constraint on permissible transplantation and is accepted on the basis of cogent argument. The present paper offers an alternative interpretation. I suggest the Altruism Requirement is a moral fiction—a kind of motivated falsehood. It is false that transplantation requires altruism. But the Requirement serves a purpose. Accepting it allows kidney donation but not kidney sale. It, in short, rationalizes the Received View.
Do States Really Sink Costs to Signal Resolve?
Authors: Altman Dan , Quek Kai
Published: March 2024

Sinking costs to signal resolve has become a vital part of how the field of international relations (IR) understands crisis bargaining. The logic of a resolved state “burning money” to distinguish itself from an unresolved state is well established in theory. But do states choose to sink costs and burn money in practice? We address the question on two fronts. First, we collect and analyze the examples of sinking costs in the mainstream IR literature. We find almost no clear-cut cases of sunk-cost signals. Second, we argue that this is because states typically prefer other signaling strategies. Rather than burning money, states can expend those resources more constructively. In particular, states can invest in improving the probability of victory in war (“balance tilting”), or they can downpay the costs of war. We conclude that balance tilting and downpaying costs plausibly explain a great deal of state behavior in peacetime, in crises, and even in wartime.
A rare case of colorectal cancer metastasis to the pancreas: a case report
Authors: Eghlimi Hesameddin , Mirzadeh Moein , Movahedi Hamidreza , Tabrizi Tala
Published: March 2024

Colon cancer is the third leading cause of cancer worldwide. On presentation, 20% of patients will have metastatic disease, and the most common sites for metastatic colon cancer are liver, lung, and peritoneum. Our patient was a 55-year-old man with a history of rectal adenocarcinoma cancer and colectomy surgery for the past 2 years, who had presented changes in bowel movements, rectal bleeding and thin. In the new visit and positron emission tomography-computed tomography scan, the results showed that there are two ill-defined foci of increased FDG (F-fluorodeoxyglucose) uptake in the body (metabolic diameter = 26 mm, SUVmax = 7.8) and tail (metabolic diameter = 13 mm, SUVmax = 7.4) of the pancreas gland, persisting on delayed images. Colon cancer metastasis to the pancreas is rare. The presence of masses in both the colon and pancreas could be a result of metastasis from the pancreas to the colon, metastasis from the colon to the pancreas, or synchronous primary cancers.
(O-09) VARIATION IN MICROSURGICAL TECHNIQUE FOR VASECTOMY REVERSAL: EXPERIENCE FROM A UNIVERSITY HOSPITAL IN RIO DE JANEIRO
Authors: Crelier G M , Viterbo R G , Heleno H A , Nunes D P , Schiavini J L , Filho RdTF , Lara C M C , Junior H R J , Damião R
Published: March 2024

Introduction/Objective

Vasectomy is a widely performed male sterilization surgery with rapid recovery. In Brazil, it is carried out following legal criteria for family planning. Vasectomy reversal is a procedure with a high success rate and is considered a cost-effective option compared to other fertility techniques. The microsurgical technique, developed in 1975, is widely adopted for reconstructing the vas deferens. Vasovasostomy is the gold standard technique, using non-absorbable sutures (9-0 or 10-0). The aim of this study is to correlate the literature's results with those achieved through the microsurgical technique employed at the Pedro Ernesto University Hospital.

Method

This study was a retrospective and descriptive analysis of medical records and a review of the literature on a surgical technique. We analyzed 56 cases performed between January 2012 and December 2022 at the Pedro Ernesto University Hospital. Additionally, scientific articles published between 1999 and 2022 were collected. Surgeries were performed under general or spinal anesthesia, using a single-layer technique with Prolene 7-0 sutures. All patients underwent sperm analysis at 1, 3, and 6 months postoperatively.

Results

A total of 56 vasectomy reversals were performed in patients with an average age of 42.91 years and an average interval of 7.65 years between vasectomy and reversal. The patency rate was 82.14%, and the pregnancy rate among those who were successfully reversed was 15.22%. Reversal was more successful (87.18% patency and 25% pregnancy) in patients with an interval of less than 10 years between surgeries.

Conclusion

The results of 56 vasectomy reversals by vasovasostomy using the modified microsurgical technique applied at the Pedro Ernesto University Hospital demonstrated satisfactory patency and pregnancy rates, closely matching those reported in the literature. The technique proved to be effective and safe, with no significant complications.

Financing

No conflict.
(O-17) INCIDENCE OF CLIMACTURIA IN MEN WITH SEXUAL DYSFUNCTION AFTER RADICAL PROSTATECTOMY
Authors: Daher Carneiro Gamberini P , Ribeiro Filho H , Afonso Teixeira T , Pedrenho Neto R , Heggendorn Sayao R , Barbosa Neto C , Bessa Junior J , Hallak J , Luedy Amoedo F , Chiesa Gouveia Nascimento B
Published: March 2024

Introduction and Purpose

Climacturia is defined as the involuntary loss of urine at the time of orgasm. Many series report incidences of climacturia greater than 50%. Even so, it remains a little-recognized symptom.

Our objective was to describe the incidence and characteristics of climacturia in patients undergoing RP in follow-up for erectile dysfunction (ED).

Method

We performed a retrospective analysis of a prospectively maintained database of men after RP with complaints of refractory ED. Patients seen in the sexual medicine group, from June 2017 to March 2021, underwent a protocol consultation that asked about the presence of climacturia, its frequency, intensity and association with discomfort. Other factors such as the presence of stress urinary incontinence (SUI), the presence of arousal incontinence (AI) and demographic data were also recorded. Patients were also asked if they had received guidance on the possibility of having climacturia in the preoperative guidelines.

Results

Sixty patients were evaluated, with a mean age of 68 (±6.15) years. Climaturia at some point was reported by 40 patients (66.6%). Of these, 65% reported it occurring rarely or occasionally, while 35% reported it occurring frequently. The presence of AI was 26.3%, with all these patients reporting associated discomfort. In general, 50% reported that climacturia caused significant discomfort, while only 17.5% perceived discomfort from partnerships. The majority (93.3%) stated that they had not been previously warned about the possibility of this condition. Among patients who had climacturia, 16.6% had associated SUI, but this association was not statistically significant.

Conclusion

This preliminary analysis is one of the first to assess the Brazilian reality of the frequency of post-RP climacturia, corroborating the high incidence, impact on sexual life and lack of preoperative guidance. Its recognition is essential for better counseling to patients.

Financing

No conflict.
(O-22) EPIDEMIOLOGICAL PROFILE OF PATINTS UNDERGOING VASECTOMY REVERSATION AT PEDRO ERNESTO UNIVERSITY HOSPITAL
Authors: Crelier G M , Vasconcelos C V O , Rosa KOd , Schiavini J L , Filho RdTF , Lara C M C , Junior H R J , Damião R
Published: March 2024

Introduction

Review of vasectomy reversal cases operated in the Urology department of HUPE. From January 2012 to January 2023, 61 vasectomy reversals were performed at Hospital Universitário Pedro Ernesto to correct obstructive azoospermia, with patients' ages ranging from 33 to 70 years and vasectomy time ranging from 2 to 15 years. Patients, except those who did not return for followup despite instructions, were followed up on an outpatient basis with sperm analysis 30 days after surgery and then every six months until the end of follow-up. Among the 42 patients who maintained outpatient follow-up (68% of the total), our casuistry presents 31 reverted patients (73% of this group), that is, with viable spermatozoa present in the spermogram. Of these, 4 patients managed to generate a pregnancy (12% of the reverted ones), with children still alive to date, 5 are no longer trying for personal reasons (16% of the reverted ones), and 22 are still trying (70% of the reverted ones). 11 patients were unsuccessful in reversal (26% of those who followed up). 19 patients lost outpatient follow-up (32% of the total).

Objectives

To observe the epidemiology of operated patients, analyzing the effectiveness of the procedure and understanding the fate of operated patients.

Methods

Work without control group, case series.

Results

High reversal rate, but with a low pregnancy rate and significant rate of loss to outpatient followup.

Conclusion

Through the analytical observation of epidemiology, outline conducts mainly regarding the outpatient follow-up of patients, given the high rate of loss to follow-up.

Financing

No conflict.