Miracle-dz/UniFAR-FTUs huggingface dataset:
Laparoscopy offers better clinical outcomes and long-term survival in patients with right colon cancer: experience from national cancer center

Purpose Laparoscopic approach to colonic tumor requires skill set and resources to be established as routine standard of care in most centers around the world. It presents particular challenge in country like Pakistan due to economic constrain and lack of teaching and training opportunities available for surgeons to be trained to deliver such service. The aim of this study is to look into changing practice of our institution from conventional approach of open to laparoscopic surgery for right colon cancer. Methods Consecutive patients between January 2010 to December 2018 who presented to Shaukat Khanum Memorial Cancer Hospital and Research Centre with diagnosis of right colon (cecum, ascending and transverse colon) adenocarcinoma and underwent surgical resections were included in this study. Results A total of 230 patients with adenocarcinoma of the right colon underwent curative resections during the study period. Of these, 141 patients (61.3%) underwent laparoscopic surgery while open resection was performed in 89 patients (38.7%). Five-year disease-free survival (DFS) of patients with American Joint Committee on Cancer (AJCC) stage III (80.9% vs. 54.8%, P = 0.021) was significantly better if these patients underwent laparoscopic surgery while a trend toward better DFS (96.7% vs. 84.1%, P = 0.111) was also observed in AJCC stage II patients, although this difference was not significant. Conclusion This study demonstrates the adoption of a laparoscopic approach for right colon cancer over 10 years. With a standardized approach and using the principle of oncological surgery, we incorporated this in our minimally invasive surgery practice at our institution.
CMOS Time-to-Digital Converters for Biomedical Imaging Applications

Time-to-digital converters (TDCs) are high-performance mixed-signal circuits capable of timestamping events with sub-gate delay resolution. As a result of their high-performance, in recent years TDCs were integrated in complementary metal-oxide-semiconductor (CMOS) technology with highly sensitive photodetectors known as single-photon avalanche diodes (SPADs), to form digital silicon photomultipliers (dSiPMs) and SPAD imagers. Time-resolved SPAD-based sensors are capable of detecting the absorption of a single photon and timestamping it with picosecond resolution. As such, SPAD-based sensors are very useful in the field of biomedical imaging, using time-of-flight (ToF) information to produce data that can be used to reconstruct high-quality biological images. Additionally, the capability of integration in standard CMOS technologies, allows SPAD-based sensors to provide high-performance, while maintaining low cost. In this paper, we present an overview of fundamental TDC principles, and an analysis of state-of-the-art TDCs. Furthermore, the integration of TDCs into dSiPMs and SPAD imagers will be discussed, with an analysis of the current results of TDCs in different biomedical imaging applications. Finally, several important research challenges for TDCs in biomedical imaging applications are presented.
Geographic Variation in Photoperiodic Response for Induction of Pseudopupal Diapause in Epicauta gorhami (Coleoptera: Meloidae)

Abstract Geographical variations in the threshold of environmental cues for diapause induction are important in understanding the life history strategy of insects. Larvae of the bean blister beetle, Epicauta gorhami (Coleoptera: Meloidae), feed on grasshopper eggs and undergo hypermetamorphosis. They normally enter diapause as a pseudopupa (fifth instar). However, when the larvae are reared under long-day and high-temperature conditions, they do not enter pseudopupal diapause but pupate directly from the fourth instar. In addition, this insect is known to modify its photoperiodic response for induction of pseudopupal diapause depending on food availability for larvae. In this study, the larval photoperiodic responses for diapause induction were examined for three populations of E. gorhami collected from the northernmost (Morioka, 39.7°N), central (Kazo, 36.1°N), and southernmost (Takanabe, 32.1°N) parts of its distribution range, and the responses were examined under both fully fed and food-deprived (FD) conditions. Diapause incidence decreased in FD larvae for all populations in long-day conditions, and the critical day-lengths for the diapause incidence were calculated as 14.81, 13.97, and 13.99 h in the Morioka, Kazo, and Takanabe populations, respectively. The results indicate the presence of a geographical variation in larval photoperiodic response, in which diapause is induced earlier in higher latitudinal areas. From these results, together with data for developmental threshold temperature and thermal constant, the Morioka and Kazo populations were suggested to have a partial bivoltine life cycle under the conditions of extremely early oviposition season, a sufficient summer temperature, and poor larval food availability.
Inflammatory cytokines TNFα and IL-17 enhance the efficacy of cystic fibrosis transmembrane conductance regulator modulators.

Without CFTR-mediated HCO3- secretion, airway epithelia of newborns with cystic fibrosis (CF) produce an abnormally acidic airway surface liquid (ASL), and the decreased pH impairs respiratory host defenses. However, within a few months of birth, ASL pH increases to match that in non-CF airways. Although the physiological basis for the increase is unknown, this time-course matches the development of inflammation in CF airways. To learn whether inflammation alters CF ASL pH, we treated CF epithelia with TNFα and IL-17, two inflammatory cytokines that are elevated in CF airways. TNFα+IL-17 markedly increased ASL pH by upregulating pendrin, an apical Cl-/HCO3- exchanger. Moreover, when CF epithelia were exposed to TNFα+IL-17, clinically approved CFTR modulators further alkalinized ASL pH. As predicted by these results, in vivo data revealed a positive correlation between airway inflammation and CFTR modulator-induced improvement in lung function. These findings suggest that inflammation is a key regulator of HCO3- secretion in CF airways. Thus, they explain earlier observations that ASL pH increases after birth and indicate that for similar levels of inflammation, the pH of CF ASL is abnormally acidic. These results also suggest that a non-cell-autonomous mechanism, airway inflammation, is an important determinant of the response to CFTR modulators.
Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma

Cancer testis antigens (CTAs) are an extensive gene family with a unique expression pattern restricted to germ cells, but aberrantly reactivated in cancer tissues. Studies indicate that the expression (or re-expression) of CTAs within the MAGE-A family is common in hepatocellular carcinoma (HCC). However, no systematic characterization has yet been reported. The aim of this study is to perform a comprehensive profile of CTA de-regulation in HCC and experimentally evaluate the role of MAGEA3 as a driver of HCC progression. The transcriptomic analysis of 44 multi-regionally sampled HCCs from 12 patients identified high intra-tumor heterogeneity of CTAs. In addition, a subset of CTAs was significantly overexpressed in histologically poorly differentiated regions. Further analysis of CTAs in larger patient cohorts revealed high CTA expression related to worse overall survival and several other markers of poor prognosis. Functional analysis of MAGEA3 was performed in human HCC cell lines by gene silencing and in a genetic mouse model by overexpression of MAGEA3 in the liver. Knockdown of MAGEA3 decreased cell proliferation, colony formation and increased apoptosis. MAGEA3 overexpression was associated with more aggressive tumors in vivo. In conclusion MAGEA3 enhances tumor progression and should be considered as a novel therapeutic target in HCC.
Self-reported sense of purpose in life and proxy-reported behavioral and psychological symptoms of dementia in the last year of life

Abstract Objectives:Behavioral and psychological symptoms of dementia (BPSD) are among the most challenging aspects of dementia for individuals living with dementia and their caregivers. Identifying factors associated with resilience to BPSD may inform interventions to reduce them. The present research examines whether purpose in life is associated with BPSD in the last year of life. Method:Participants from the Health and Retirement Study were selected if they reported on their sense of purpose, had evidence of a memory impairment, died across the follow-up, and a proxy completed the End of Life survey that included BPSD (N = 2473). Self-reported sense of purpose was tested as a predictor of the sum of symptoms and each indivdual symptom in the last year of life. Results:Purpose in life was associated with fewer BPSD overall. Of the individual symptoms, purpose was associated with less risk of psychological symptoms, specfiically less depression, periodic confusion, uncontrolled temper, but not with motor or perceptual symptoms. Conclusion: These results are consistent with growing evidence that purpose is associated with better cognitive outcomes. Purpose may be a useful target of intervention to improve outcomes across the spectrum of dementia
Mycobacterium setense isolated from a cat with atypical mycobacterial panniculitis

Zusammenfassung Bei einer Katze wurde eine atypische mykobakterielle Pannikulitis diagnostiziert. Mittels 16S-rRNA-Gen-Sequenzanalyse ließ sich Mycobacterium setense, ein grampositives stäbchenförmiges säurefestes Bakterium der Mycobacterium fortuitum-Gruppe nachweisen, das zuvor nie bei einem erkrankten Tier isoliert werden konnte. Initial wurden Resistenzen gegen Doxycyclin und Clarithromycin festgestellt und während der Behandlung mit Pradofloxacin entwickelte sich zudem eine Resistenz gegen Fluorchinolone, bedingt durch eine Mutation im Gyrasegen gyrA (S90W-Austausch). Trotz einer langfristigen antimikrobiellen Behandlung über 33 Monate wurde keine vollständige Heilung erzielt. Bei einer atypischen mykobakteriellen Pannikulitis ist die Speziesbestimmung mit Resistenztest die Grundlage für eine adäquate Antibiose.
Defibrotide: potential for treating endothelial dysfunction related to viral and post-infectious syndromes

ABSTRACT Introduction Defibrotide (DF) is a polyribonucleotide with antithrombotic, pro-fibrinolytic, and anti-inflammatory effects on endothelium. These effects and the established safety of DF present DF as a strong candidate to treat viral and post-infectious syndromes involving endothelial dysfunction. Areas Covered We discuss DF and other therapeutic agents that have the potential to target endothelial components of pathogenesis in viral and post-infectious syndromes. We introduce defibrotide (DF), describe its mechanisms of action, and explore its established pleiotropic effects on the endothelium. We describe the established pathophysiology of Coronavirus Disease 2019 (COVID-19) and highlight the processes specific to COVID-19 potentially modulated by DF. We also present influenza A and viral hemorrhagic fevers, especially those caused by hantavirus, Ebola virus, and dengue virus, as viral syndromes in which DF might serve therapeutic benefit. Finally, we offer our opinion on novel treatment strategies targeting endothelial dysfunction in viral infections and their severe manifestations. Expert Opinion Given the critical role of endothelial dysfunction in numerous infectious syndromes, in particular COVID-19, therapeutic pharmacology for these conditions should increasingly prioritize endothelial stabilization. Several agents with endothelial protective properties should be further studied as treatments for severe viral infections and vasculitides, especially where other therapeutic modalities have failed.
Relationship between ankle varus moment during gait and radiographic measurements in patients with medial ankle osteoarthritis

Background Kinetic data obtained during gait can be used to clarify the biomechanical pathogenesis of osteoarthritis of the lower extremity. This study aimed to investigate the difference in ankle varus moment between the varus angulation and medial translation types of medial ankle osteoarthritis, and to identify the radiographic measurements associated with ankle varus moment. Methods Twenty-four consecutive patients [mean age 65.8 (SD) 8.0 years; 9 men and 15 women] with medial ankle osteoarthritis were included. Fourteen and 10 patients had the varus angulation (tibiotalar tilt angle≥3 degrees) and medial translation (tibiotalar tilt angle<3 degrees) types, respectively. All patients underwent three-dimensional gait analysis, and the maximum varus moment of the ankle was recorded. Radiographic measurement included tibial plafond inclination, tibiotalar tilt angle, talar dome inclination, and lateral talo-first metatarsal angle. Comparison between the two types of medial ankle osteoarthritis and the relationship between the maximum ankle varus moment and radiographic measurements were analyzed. Results The mean tibial plafond inclination, tibiotalar tilt angle, talar dome inclination, lateral talo-first metatarsal angle, and maximum ankle varus moment were 6.4 degrees (SD 3.3 degrees), 5.0 degrees (SD 4.6 degrees), 11.4 degrees (SD 5.2 degrees), -6.5 degrees (SD 11.7 degrees), and 0.185 (SD 0.082) Nm/kg, respectively. The varus angulation type showed a greater maximum ankle varus moment than the medial translation type (p = .005). The lateral talo-first metatarsal angle was significantly associated with the maximum ankle varus moment (p = .041) in the multiple regression analysis. Conclusion The varus angulation type of medial ankle osteoarthritis is considered to be more imbalanced biomechanically than the medial displacement type. The lateral talo-first metatarsal angle, being significantly associated with the ankle varus moment, should be considered for correction during motion-preserving surgeries for medial ankle osteoarthritis to restore the biomechanical balance of the ankle.
Expression of versican mRNA transcript to predict cardiac remodelling after myocardial infarction.

BACKGROUND Adverse left-ventricular remodelling (LVR) is defined as an increase in end-diastolic left-ventricular volume by 20% 6 months after acute myocardial infarction (AMI). LVR is associated with cardiac dysfunction, therefore deteriorating the prognosis. AIMS We aimed to compare the concentrations of messenger RNA transcripts in the peripheral blood of patients with and without LVR at 6 months. METHODS The study included 75 patients with first ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention. Whole blood concentrations of 6 transcripts were determined 24 hours after AMI using droplet digital polymerase chain reaction. The correlations between mRNA transcript expression and left ventricular ejection fraction (LVEF) and N-terminal-pro B type natriuretic peptide (NT-proBNP) concentration were evaluated. RESULTS Among 75 patients, 4 were lost to follow-up and 71 were included in the analysis. Seventeen (24%) patients developed LVR at 6 months. Versican (VCAN) mRNA expression was lower in patients who developed LVR, compared to those who did not (P = 0.02), and discriminated between these patients (area under the ROC curve 67%; P = 0.04). Expression of VCAN transcript < 75.3 normalized units predicted LVR with 71% sensitivity and 67% specificity. In a multivariable regression analysis, VCAN expression remained the only independent predictor of LVR (OR 3.475; 95% CI, 1.000-12.075; P = 0.04). CONCLUSIONS Dysregulation of VCAN expression in the acute phase of AMI may contribute to LVR at 6 months. Whether decreased expression of VCAN might be a useful tool to predict LVR in clinical practice remains to be established.
Global collapse of the dural sinuses after venous stenting in idiopathic intracranial hypertension

Lateral sinus stenoses (LSS) may represent the macroscopic evidence of the microscopic restriction in the venous CSF outflow pathway in idiopathic intracranial hypertension (IIH). 1 These stenoses seem to play a crucial role in maintaining and/or triggering the ‘vicious cycle’ of IIH. By restoring a physiological pressure gradient between the venous system and the subarachnoid space, venous sinus stenting (VSS) allows us to break this cycle and in many cases effectively relieve the symptoms related to elevated intracranial pressure (ICP). However, IIH symptoms may recur in about 10% of patients.2 In most of these relapsed cases, a stenosis of the stent-adjacent ipsilateral transverse sinus and/or of the proximal third of the superior longitudinal sinus (SLS) is found, which seems to retrigger the pathological loop of IIH. The serial changes in the appearances of the venous system after VSS in asymptomatic or mildly symptomatic patients have never been evaluated in the literature. With our institutional review board approval (IRB: CRM-2001-055), we retrospectively collected the clinical and radiological features of consecutive patients treated with VSS for IIH from January 2013 to December 2019 in our two tertiary-referral institutions. Inclusion criteria were adult patients who underwent VSS for IIH refractory to/with contraindications to medical therapy. All patients underwent a brain 3T-MRI with contrast-enhanced MR venography before and 3–6 months after stent placement. A conventional digital subtracted angiography with venous manometry was performed prior to stent placement under local anaesthesia. The area of the lumen of the dural sinuses, their minimal diameter (online supplemental figures 1 and 2) and their volume (online …
Analysis of Functional Brain Network in MDD Based on Improved Empirical Mode Decomposition With Resting State EEG Data

At present, most brain functional studies are based on traditional frequency bands to explore the abnormal functional connections and topological organization of patients with depression. However, they ignore the characteristic relationship of electroencephalogram (EEG) signals in the time domain. Therefore, this paper proposes a network decomposition model based on Improved Empirical Mode Decomposition (EMD), it is suitable for time-frequency analysis of brain functional network. On the one hand, it solves the problem of mode mixing on original EMD method, especially on high-density EEG data. On the other hand, by building brain function networks on different intrinsic mode function (IMF), we can perform time-frequency analysis of brain function connections. It provides a new insight for brain function connectivity analysis of major depressive disorder (MDD). Experimental results found that the IMFs waveform decomposed by Improved EMD was more stable and the difference between IMFs was obvious, it indicated that the mode mixing can be effectively solved. Besides, the analysis of the brain network, we found that the changes in MDD functional connectivity on different IMFs, it may be related to the pathological changes for MDD. More statistical results on three network metrics proved that there were significant differences between MDD and normal controls (NC) group. In addition, the aberrant brain network structure of MDDs was also confirmed in the hubs characteristic. These findings may provide potential biomarkers for the clinical diagnosis of MDD patients.
Vitamin D status and associated factors among HIV-infected children and adolescents on antiretroviral therapy in Kampala, Uganda

Background A high prevalence of suboptimal serum vitamin D has been reported among HIV infected children even in countries with high sunshine abundance throughout the year. Vitamin D is a potent immune modulator of innate and adaptive immune responses. Vitamin D regulates immune responses through the vitamin D receptor on CD4 cells. We aimed to determine the vitamin D status of HIV infected children and factors associated with suboptimal vitamin D. Methods This was a cross sectional study. We enrolled children aged between 6 months and 12 years attending an outpatient paediatric HIV clinic. Serum 25-hydroxyvitamin D (25(OH)D) was measured using the electrochemoluminisence method. Suboptimal vitamin D was defined as 25(OH)D <30 ng/ml, vitamin D insufficiency and deficiency were 21–29 ng/ml and <20 ng/ml respectively. Anthropometry, physical exam and medical history were documented. Logistic regression was performed. Results We enrolled 376 children with mean age (sd) 8.05 years (3.03), a median (IQR) duration of ART of 5.9 years (3.2–8.4). Majority of the children (64%) had been exposed to non nucleoside reverse transcriptase inhibitors (NNRTIs). A third were severely immunosuppressed (CD4% ≤15%) at ART initiation. At the time of the study, the majority (89%) were virologically suppressed (VL <1000 copies/ml). Prevalence of 25(OH)D <30 ng/ml was 49 (13%) of 375 participants and 11 (3%) had 25(OH)D <20 ng/ml. Lopinavir/ritonavir regimen was independently associated with 25(OH)D <30 ng/ml; OR 0.27 CI (0.13–0.57), p value-0.002. Serum 25(OH)D <20 ng/ml was associated with CD4 count ≤15% at ART initiation OR 6.55(1.30–32.9), p value—0.023 and use of NNRTIs; OR 10.9(1.22–96.2), p value—0.03. Conclusion We found a low prevalence of suboptimal vitamin D compared to earlier reports. Severe immunosuppression at ART initiation and use of NNRTIs increases odds of deficiency. Vitamin D supplementation should be considered in severely immunosuppressed children initiating ART.
The influence of Swirl and Tumble on the combustion, emissions formation and heat transfer in Diesel Dual Fuel engines

With the increasing focus on the link between the increasing consumption of fossil fuel and rising concentration levels of carbon dioxide, research into alternative fuels and engine concepts is intensifying, where Diesel Dual Fuel is the concept investigated during this Thesis. Specifically, the impact of the rotational movements Swirl and Tumble on the combustion, emissions formation and heat transfer in a port injected Diesel Dual Fuel is examined. The results show that Swirl and Tumble to varying degree affect the flame propagation as well as how the emissions formation of unburned hydrocarbons, originating from incomplete combustion, depend upon crevices or flame quenching depending on test conditions. The results also show that the Swirl and Tumble movements influences the after-oxidation of unburned hydrocarbons to different extent and its mechanisms depending on the test conditions. For crevice-geared tests the absence of Swirl movement at Swirl 1 leads to unburned hydrocarbons remaining along the liner during the expansion stroke, thus escaping oxidation. For all tests the increasing heat transfer with higher Swirl leads to reduced after-oxidation. At the maximum Swirl 7 the more advanced, stable and intense combustion compensates for the reduced after-oxidation resulting from the lower exhaust gas temperatures. For leaner test conditions, the low turbulence at Swirl 3.8, Tumble 1.25 results in an extended ignition delay, which coincides with an unstable combustion and very high levels of unburned hydrocarbons. Considerably lower levels of unburned hydrocarbons are seen at Swirl 2.5, Tumble 1.2 where a rather late yet stable combustion benefits from the lower cooling losses and thus improved after-oxidation. Similarly low levels are seen at Swirl 3.8, Tumble 4 where the Tumble shortens the ignition delay duration and the after-oxidation is equally beneficial.