bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between glycolysis markers and prognosis of liver cancer: a systematic review and meta-analysis
Authors: Wang Boqin , Pu Rong
Published: December 2023

Background

In recent years, the capacity of tumor cells to maintain high levels of glycolysis, even in the presence of oxygen, has emerged as one of the main metabolic traits and garnered considerable attention. The purpose of this meta-analysis is to investigate the prognostic value of glycolysis markers in liver cancer.

Methods

PubMed, Embase, and Cochrane Library databases were searched for articles on glycolytic marker expression levels associated with the prognosis of liver cancer until April 2023. Stata SE14.0 was used to calculate the aggregate hazard ratios and 95% confidence intervals.

Results

Thirty-five studies were included. The worse overall survival (OS) (P < 0.001), disease-free survival (DFS) (P = 0.001), recurrence-free survival (RFS) (P = 0.004), and time to recurrence (TTR) (P < 0.001) were significantly associated with elevated expression of glycolysis markers. Higher expression of PKM2 (P < 0.001), STMN1 (P = 0.002), MCT4 (P < 0.001), GLUT1 (P = 0.025), HK-2 (P < 0.001), and CA9 (P < 0.001) were significantly related to shorter OS. Increased levels of PKM2 (P < 0.001), CA9 (P = 0.005), and MCT4 (P < 0.001) were associated with worse DFS. Elevated PKM2 expression (P = 0.002) was also associated with poorer RFS in hepatocellular carcinoma patients. GLUT2 expression was not correlated with the prognosis of liver cancer (P = 0.134).

Conclusions

Elevated expression of glycolysis markers was associated with worse OS, DFS, RFS, and TTR in patients with liver cancer. Therefore, these glycolysis markers could serve as potential prognostic markers and therapeutic targets in liver cancer.

Trial registration

PROSPERO registration: CRD42023469645.
Mitochondrion-targeted carboxymethyl chitosan hybrid nanoparticles loaded with Coenzyme Q10 protect cardiac grafts against cold ischaemia‒reperfusion injury in heart transplantation
Authors: Yuan Shun , Che Yanjia , Wang Zhiwei , Xing Kai , Xie Xiaoping , Chen Yuanyang
Published: December 2023

Background

Heart transplantation (HT) has been approved as an optimal therapeutic regimen for patients with terminal-stage cardiac failure. However, cold ischaemia‒reperfusion (I/R) injury remains an unavoidable and outstanding challenge, which is a major factor in early graft dysfunction and an obstacle to long-term survival in HT. Cold I/R injury induces cardiac graft injury by promoting mitochondrial dysfunction and augmenting free radical production and inflammatory responses. We therefore designed a mitochondrion-targeted nanocarrier loaded with Coenzyme Q10 (CoQ10) (CoQ10@TNPs) for treatment of cold I/R injury after cardiac graft in a murine heterotopic cardiac transplantation model.

Methods

Hybrid nanoparticles composed of CaCO3/CaP/biotinylated-carboxymethylchitosan (CaCO3/CaP/BCMC) were synthesized using the coprecipitation method, and the mitochondria-targeting tetrapeptide SS31 was incorporated onto the surface of the hybrid nanoparticles through biotin-avidin interactions. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis were used for characterisation. In vitro, the hypoxia-reoxygenation model of H9c2 cells was employed to replicate in vivo cold I/R injury and treated with CoQ10@TNPs. The impact of CoQ10@TNPs on H9c2 cell injury was assessed by analysis of oxidative damage and apoptosis. In vivo, donor hearts (DHs) were perfused with preservation solution containing CoQ10@TNPs and stored in vitro at 4 °C for 12 h. The DHs were heterotopically transplanted and analysed for graft function, oxidative damage, apoptosis, and inflammatory markers 1 day post-transplantation.

Results

CoQ10@TNPs were successfully synthesized and delivered CoQ10 to the mitochondria of the cold ischaemic myocardium. In vitro experiments demonstrated that CoQ10@TNPs was taken up by H9c2 cells at 4 °C and localized within the mitochondria, thus ameliorating oxidative stress damage and mitochondrial injury in cold I/R injury. In vivo experiments showed that CoQ10@TNPs accumulated in DH tissue at 4 °C, localized within the mitochondria during cold storage and improved cardiac graft function by attenuating mitochondrial oxidative injury and inflammation.

Conclusions

CoQ10@TNPs can precisely deliver CoQ10 to the mitochondria of cold I/R-injured cardiomyocytes to effectively eliminate mitochondrial reactive oxygen species (mtROS), thus reducing oxidative injury and inflammatory reactions in cold I/R-injured graft tissues and finally improving heart graft function. Thus, CoQ10@TNPs offer an effective approach for safeguarding cardiac grafts against extended periods of cold ischaemia, emphasizing the therapeutic potential in mitigating cold I/R injury during HT. These findings present an opportunity to enhance existing results following HT and broaden the range of viable grafts for transplantation.
Amelioration of experimental autoimmune encephalomyelitis by in vivo reprogramming of macrophages using pro-resolving factors
Authors: Gauthier Thierry , Martin-Rodriguez Omayra , Chagué Cécile , Daoui Anna , Ceroi Adam , Varin Alexis , Bonnefoy Francis , Valmary-Degano Séverine , Couturier Mélanie , Behlke Susanne , Saas Philippe , Cartron Pierre-François , Perruche Sylvain
Published: December 2023

Background

Reinstating inflammation resolution represents an innovative concept to regain inflammation control in diseases marked by chronic inflammation. While most therapeutics target inflammatory molecules and inflammatory effector cells and mediators, targeting macrophages to initiate inflammation resolution to control neuroinflammation has not yet been attempted. Resolution-phase macrophages are critical in the resolution process to regain tissue homeostasis, and are programmed through the presence and elimination of apoptotic leukocytes. Hence, inducing resolution-phase macrophages might represent an innovative therapeutic approach to control and terminate dysregulated neuroinflammation.

Methods

Here, we investigated if the factors released by in vitro induced resolution-phase macrophages (their secretome) are able to therapeutically reprogram macrophages to control neuroinflammation in the model of experimental autoimmune encephalomyelitis (EAE).

Results

We found that injection of the pro-resolutive secretome reduced demyelination and decreased inflammatory cell infiltration in the CNS, notably through the in vivo reprogramming of macrophages at the epigenetic level. Adoptive transfer experiments with in vivo or in vitro reprogrammed macrophages using such pro-resolutive secretome confirmed the stability and transferability of this acquired therapeutic activity.

Conclusions

Overall, our data confirm the therapeutic activity of a pro-resolution secretome in the treatment of ongoing CNS inflammation, via the epigenetic reprogramming of macrophages and open with that a new therapeutic avenue for diseases marked by neuroinflammation.
The eco-ethical contribution of Menico Torchio – a forgotten pioneer of European Bioethics
Authors: Rincic Iva , Muzur Amir , Richie Cristina
Published: December 2023

Background

In 1926, Fritz Jahr described bio-ethics (German: bio-ethik) as “the assumption of moral obligations not only towards humans, but towards all forms of life.” Jahr summarized his philosophy by declaring, “Respect every living being on principle as an end in itself and treat it, if possible, as such!.” Bioethics was thus originally an ethical system concerned with the “problems of interference with other living beings… and generally everything related to the balance of the ecosystem” according to the 1978 Encyclopedia of Bioethics. This definition was predicated on the work of Fritz Jahr, Menico Torchio, and Van Rensselaer Potter.

Methods

In order to proceed with depthful analysis of the origin and major bioethical flare up, we will use critical analysis of existing literature, followed by a study trip to relevant bioethical localities (collecting photo and other documentations regarding Menico Torchio).

Results

While Jahr and Potter are typically given intellectual credit for developing the field of bioethics, the eco-ethical contributions of Menico Torchio have been forgotten.This article will first trace the origins of “bioethics” – now commonly bifurcated into “biomedical ethics” and “environmental bioethics.” The former was developed by Tom Beauchamp from the Philosophy Department and James Childress of the Religious Studies department at Georgetown University and is based on principlism, with a narrow focus on medical settings. The latter addresses the environmental impact of the medical industry and climate change health hazards. Second, we will present a panorama of Torchio’s significant intellectual contribution to bioethics. Menico Torchio’s concept of bioethics synthesized work of both Jahr and Potter, advocating “the need to expand our ethical obligations and embrace the most developed groups of animals, not only physically but also psychologically.” Third, we will reflect on the lasting legacy of “bioethics” on biomedical and environmental bioethics today. Thematic elements such as interconnectedness of planetary health and human health, dedication to living in harmony with nature, and emphasis on systems and symbiosis remain unchanged from the legacy of Tochio onward.

Conclusion

Our conclusion will underscore the necessity of understanding the connections between planetary, environmental, and human health.
Hemostatic radiotherapy in clinically significant tumor-related bleeding: excellent palliative results in a retrospective analysis of 77 patients
Authors: Guhlich Manuel , Maag Teresa Esther , Dröge Leif Hendrik , Hille Andrea , Donath Sandra , Bendrich Stephanie , Schirmer Markus Anton , Nauck Friedemann , Leu Martin , Riggert Joachim , Gallwas Julia , Rieken Stefan
Published: December 2023

Background

Significant bleeding of tumor sites is a dreaded complication in oncological diseases and often results in clinical emergencies. Besides basic local and interventional procedures, an urgent radiotherapeutic approach can either achieve a bleeding reduction or a bleeding stop in a vast majority of patients. In spite of being used regularly in clinical practice, data reporting results to this therapy approach is still scarce.

Methods

We retrospectively analyzed 77 patients treated for significant tumor-related bleeding at our clinic between 2000 and 2021, evaluating treatment response rate, hemoglobin levels, hemoglobin transfusion necessity, administered radiotherapy dose and overall survival.

Results

Response rate in terms of bleeding stop was 88.3% (68/77) in all patients and 95.2% (60/63) in the subgroup, wherein radiotherapy (RT) was completed as intended. Hemoglobin transfusions decreased during treatment in a further subgroup analysis. Median overall survival (OS) was 3.3 months. Patients with primary tumors (PT) of the cervix (carcinoma of the cervix, CC) or endometrium (endometrioid carcinoma, EDC) and patients receiving the full intended RT dose showed statistically significant better OS in a multivariable cox regression model. Median administered dose was 39 Gy, treatment related acute toxicity was considerably low.

Conclusions

Our data show an excellent response rate with a low toxicity profile when administering urgent radiotherapy for tumor related clinically significant bleeding complications. Nonetheless, treatment decisions should be highly individual due to the low median overall survival of this patient group.
Elbow dislocation approach for complex elbow fractures: a cadaveric study
Authors: Liu Yang , Gao Yuling , Xu Xiaopei , Zhao Yanrui , Wang Hanzhou , Sun Qingnan , Zhao Binzhi , Wang Siyuan , Zhou Junlin
Published: December 2023

Background

Approach need to be considered when surgeons dealt with complex elbow injuries and the choice of the approach is a challenge for surgeons due to the complex anatomy. On the basis of releasing the lateral collateral ligament, we modified the dislocation technique to pursue the superior exposure including not only the distal humeral surface but also the anterior facet of the coronoid process.

Methods

A total of 4 cadaver specimens and 8 elbows were included in the study. Each cadaver provided one elbow for either the elbow dislocation approach or the posterior olecranon approach. The exposed distal articular surface of humerus, humeral capitulum, humeral trochlea, anterior trochlea of distal humerus, posterior trochlea of distal humerus and the ulnar coronoid process surface were marked by image J software and calculated for a comparison for each surgical approach.

Results

The total distal humeral surface was exposed as a median of 98.2 (97.6, 99.6)% and 62.0 (58.3, 64.5)% for the elbow dislocation approach and the olecranon osteotomy approach (P < 0.001), the capitulum 100% and 32.4 (28.0, 39.2)% (P < 0.001), the trochlea 93.2(90.1, 96.9)% and 72.5 (65.2, 78.8)% (P < 0.001), the anterior trochlear articular surface 96.0(93.0, 97.4)% and 50.3 (43.6, 59.1)% (P < 0.001), the posterior trochlear articular surface 95.4 (93, 100)% and 100% (P = 0.76) and the articular surface of the coronoid process of ulna 71.3 (66.0, 74.2)% and 0% (P < 0.001).

Conclusion

For complex elbow fractures, the technique of elbow dislocation provides complete exposure of the distal humerus surface and a significant portion of the coronoid process surface, facilitating direct visualization for reduction and fixation.

Level of evidenceAnatomy Study; Cadaver Dissection.
Automated and app-based activation of first responders for prehospital cardiac arrest: an analysis of 16.500 activations of the KATRETTER system in Berlin
Authors: Pommerenke C. , Poloczek S. , Breuer F. , Wolff J. , Dahmen J.
Published: December 2023

Background

Bystander CPR is one of the main independent factors contributing to better survival after out-of-hospital cardiac arrest. Simultaneously, the rate of bystander CPR in Germany is below the European average. First responder applications (apps) contribute to reducing the time period without CPR (no-flow time) until professional help can arrive on-scene.

Methods

The KATRETTER app was introduced in Berlin as one of the first apps in Europe which do not require any medical qualifications to register as a first responder. The activation of volunteer first responders for suspected cardiac arrest cases through the Berlin Emergency Medical Services integrated control center was evaluated based on data collected between 16 Oct 2020 and 16 Oct 2022. Our descriptive analysis includes the number of registered first responders, number of activations, the number and percentages of accepted activations, as well as all reports where first responders arrived at the scene.

Results

As of 15 Oct 2022, a total of 10,102 first responders were registered in the state of Berlin. During this specified period, there were 16.505 activations of the system for suspected out-of-hospital cardiac arrest. In 38.4% of the accepted cases, first responders documented patient contact, and in 34.6% of cases with patient contact, CPR was performed. Only 2% of registered first responders did not have any medical qualifications.

Conclusions

Smartphone-based first responder applications should not be understood as a means of alerting professional help, but rather like a digitally amplified “call for help” in the vicinity of an emergency location. A large number of first responders can be recruited within 24 months, without large-scale public relations work necessary. No qualifications were required to become a first responder, contributing to a low-threshold registration process with the effect of a more widespread distribution of the app and cost reduction during implementation.
RAPIDIRON Trial follow-up study — the RAPIDIRON-KIDS Study: protocol of a prospective observational follow-up study
Authors: Derman Richard J. , Bellad Roopa B. , Bellad Mrutyunjaya B. , Bradford-Rogers Jesse , Georgieff Michael K. , Aghai Zubair H. , Thind Simal , Auerbach Michael , Boelig Rupsa , Leiby Benjamin E. , Short Vanessa , Yogeshkumar S. , Charantimath Umesh S. , Somannavar Manjunath S. , Mallapur Ashalata A. , Pol Ramesh , Ramadurg Umesh , Sangavi Radha , Peerapur Basavaraj V. , Banu Nasima , Patil Praveen S. , Patil Amaresh P. , Roy Subarna , Vastrad Phaniraj , Wallace Dennis , Shah Hemang , Goudar Shivaprasad S.
Published: December 2023

Background

Anemia is a worldwide problem with iron deficiency being the most common cause. When anemia occurs in pregnancy, it increases the risk of adverse maternal, fetal, and postnatal outcomes. It induces preterm births and low birth weight (LBW) deliveries, long-term neurodevelopmental sequelae, and an increased risk of earlier onset of postnatal iron deficiency. Anemia rates are among the highest in South Asia, and India’s National Family Health Survey (NFHS-5) for 2019–2021 indicated that over half of pregnant women, and more than 65% of children, in the country are classified as anemic (Sciences IIfP, National Family Health Survey-5, 2019–21, India Fact Sheet). In 2021, the parent RAPIDIRON Trial (Derman et al., Trials 22:649, 2021) was initiated in two states in India, with the goal of assessing whether a dose of intravenous (IV) iron given to anemic women during early pregnancy results in a greater proportion of participants with normal hemoglobin concentrations in the third trimester and a lower proportion of participants with LBW deliveries compared to oral iron. As a follow-up to the RAPIDIRON Trial, the RAPIDIRON-KIDS Study will follow the offspring of previously randomized mothers to assess, neurobehavioral, hematological, and health outcomes.

Methods

This prospective observational cohort study will follow a subset of participants previously randomized as part of the RAPIDIRON Trial and their newborns. Study visits occur at birth, 6 weeks, 4 months, 12 months, 24 months, and 36 months and include blood sample collection with both maternal and infant participants and specific neurobehavioral assessments conducted with the infants (depending on the study visit). The primary outcomes of interest are (1) infant iron status as indicated by both hemoglobin and ferritin (a) at birth and (b) at 4 months of age and (2) the developmental quotient (DQ) for the cognitive domain of the Bayley Scales of Infant Development Version IV (BSID-IV) at 24 months of age.

Discussion

This RAPIDIRON-KIDS Study builds upon its parent RAPIDIRON Trial by following a subset of the previously randomized participants and their offspring through the first 3 years of life to assess neurodevelopmental and neurobehavioral (infants, children), hematological, and health outcomes.

Trial registration

ClinicalTrials.gov NCT05504863, Registered on 17 August 2022. Clinical Trials Registry – India CTRI/2022/05/042933. Registered on 31 May 2022.
Accidental portal vein catheterization during pleural drainage catheter insertion: a case report
Authors: Zoghoul Sohaib , Al‑Hashimi Israa , Aldebyani Qayed , Kassamali Rahil , Omar Ahmed , Barah Ali
Published: December 2023

Background

Iatrogenic portal vein (PV) injuries following pleural drainage catheter (PDC) insertion are rare but life-threatening. This case report emphasizes the importance of prompt recognition and effective interventional radiology (IR) management.

Case presentation

A 38-year-old Asian male, admitted for a non-ST-segment elevation myocardial infarction, suffered a critical PV injury during PDC insertion, leading to rapid clinical deterioration. The IR team conducted a portogram, retrieved the catheter, and successfully executed an embolization procedure. The patient's recovery, confirmed through imaging and improving liver function tests, enabled discharge with follow-up instructions.

Conclusions

This case highlights the clinical significance of promptly recognizing and effectively managing iatrogenic PV injuries during PDC insertion, with the pivotal role of IR. Collaboration between IR and surgical teams is crucial for optimizing patient outcomes.
MT2DInv-Unet: A 2D magnetotelluric inversion method based on deep-learning technology
Authors: Pan Kejia , Ling Weiwei , Zhang Jiajing , Zhong Xin , Ren Zhengyong , Hu Shuanggui , He Dongdong , Tang Jingtian
Published: December 2023

Traditional gradient-based inversion methods usually suffer from the problems of falling into local minima and relying heavily on initial guesses. Deep-learning methods have received increasing attention due to their excellent nonlinear fitting ability. However, given the recent application of deep-learning methods in the field of magnetotelluric (MT) inversion, there are currently challenges associated with achieving high inversion resolution and extracting sufficient features. We develop a neural network model (called MT2DInv-Unet) based on the deformable convolution for 2D MT inversion to approximate the nonlinear mapping from the MT response data to the resistivity model. The deformable convolution is achieved by adding an offset to each sample point of the conventional convolution operation, which extracts hidden relationships and allows the flexible adjustment of the size and shape of the feature region. Meanwhile, we design the network structure with multiscale residual blocks, which effectively extract the multiscale features of the MT response data. This design not only enhances the network performance but also alleviates issues such as vanishing gradients and network degradation. The results of synthetic models indicate that our network inversion method has stable convergence, good robustness, and generalization performance, and it performs better than the fully convolutional neural network and U-Net network. Finally, the inversion results of field data show that MT2DInv-Unet can effectively obtain a reliable underground resistivity structure and has a good application prospect in MT inversion.
Self-supervised, active learning seismic full-waveform inversion
Authors: Colombo Daniele , Turkoglu Ersan , Sandoval-Curiel Ernesto , Alyousuf Taqi
Published: December 2023

A novel recursive, self-supervised machine-learning (ML) inversion scheme is developed. It is applied for fast and accurate full-waveform inversion of land seismic data. ML generalization is enhanced by using virtual super gathers (VSGs) of field data for training. These are obtained from midpoint-offset sorting and stacking after applying surface-consistent corrections from the decomposition of the transmitted wavefield. The procedure implements reinforcement learning concepts by adopting an inversion agent to interact with the environment and explore the model space under a data misfit optimization policy. The generated parameter distributions and related forward responses are used as new training samples for supervised learning. The active learning (AL) paradigm is further embedded in the procedure, for which queries on data diversity and uncertainty are used to generate fully informative reduced sets for training. The procedure is recursive. At each cycle, the physics-based inversion is coupled to the ML predictions via penalty terms that promote a long-term data misfit reduction. The resulting self-supervised, AL, physics-driven deep-learning inversion generalizes well with field data. The method is applied to perform full-waveform inversion (FWI) of a complex land seismic data set characterized by transcurrent faulting and related structures. High signal-to-noise VSGs are inverted with a 1.5D Laplace-Fourier FWI scheme. The AL inversion procedure uses a small fraction of data for training while achieving sharper velocity reconstructions and a lower data misfit when compared with previous results. AL FWI is highly generalizable and effective for land seismic velocity model building and for other inversion scenarios.
Rogue wave patterns of the Fokas-Lenells equation
Authors: Yan Xue-Wei , Chen Yong
Published: December 2023

In this work, we study the high-order rogue wave solution for the Fokas-Lenells equation using the Kadomtsev-Petviashvili (KP) reduction method. These rogue wave patterns consist of triangle, pentagon, heptagon, nonagon, which are analytically described by the root structures of the Yablonskii-Vorob'ev polynomial hierarchy. On the other hand, we also report the other types of rogue wave patterns including heart-shaped, fan-shaped, two-arc+triangle, arc+pentagon, etc., which are analytically described by the root structures of Adler-Moser polynomials. These polynomials are the generalizations of the Yablonskii-Vorob'ev polynomial hierarchy, because of the arbitrariness of complex parameter

. In addition, these rogue wave patterns are formed by the Peregrine solitons undergoing dilation, rotation, stretch, shear and translation. We also compare the prediction solutions with the corresponding true solutions and show the good consistency between them.
Proteoglycan inhibition of canonical BMP-dependent cartilage maturation delays endochondral ossification
Authors: Koosha Elham , Brenna Connor T. A. , Ashique Amir M. , Jain Niteesh , Ovens Katie , Koike Toshiyasu , Kitagawa Hiroshi , Eames B. Frank
Published: December 2023

During endochondral ossification, chondrocytes secrete a proteoglycan (PG)-rich extracellular matrix that can inhibit the process of cartilage maturation, including expression of Ihh and Col10a1. Because bone morphogenetic proteins (BMPs) can promote cartilage maturation, we hypothesized that cartilage PGs normally inhibit BMP signalling. Accordingly, BMP signalling was evaluated in chondrocytes of wild-type and PG mutant (fam20b−/−) zebrafish and inhibited with temporal control using the drug DMH1 or an inducible dominant-negative BMP receptor transgene (dnBMPR). Compared with wild type, phospho-Smad1/5/9, but not phospho-p38, was increased in fam20b−/− chondrocytes, but only after they secreted PGs. Phospho-Smad1/5/9 was decreased in DMH1-treated or dnBMPR-activated wild-type chondrocytes, and DMH1 also decreased phospho-p38 levels. ihha and col10a1a were decreased in DMH1-treated or dnBMPR-activated chondrocytes, and less perichondral bone formed. Finally, early ihha and col10a1a expression and early perichondral bone formation of fam20b mutants were rescued with DMH1 treatment or dnBMPR activation. Therefore, PG inhibition of canonical BMP-dependent cartilage maturation delays endochondral ossification, and these results offer hope for the development of growth factor therapies for skeletal defects of PG diseases.
Η αγορά των εφαρμογών κινητής υγείας
Authors: Χατζηπαύλου Ιωάννης
Published: December 2023

Η παρούσα διατριβή πραγματεύεται τη δημιουργία ενός μοντέλου ταξινόμησης των εφαρμογών της κινητής υγείας (m-health) που συναντώνται στα καταστήματα εφαρμογών. Οι εφαρμογές κινητής υγείας είναι ένας κλάδος που εντάσσεται στα πληροφοριακά συστήματα και έχει παρουσιάσει τεράστια ανάπτυξη τα τελευταία χρόνια κυρίως λόγω των τεχνολογικών εξελίξεων, κυρίως με την έλευση των έξυπνων κινητών τηλεφώνων (smartphones) και την ανάπτυξη και εξέλιξη των κινητών δικτύων. Αυτή η έρευνα επιδιώκει να δημιουργήσει μια ταξινόμηση η οποία θα επιφέρει διαφάνεια στις σχέσεις μεταξύ των εμπλεκομένων οντοτήτων που αλληλεπιδρούν στο οικοσύστημα των εφαρμογών κινητής υγείας. Για την επίτευξη αυτού του στόχου, η ερευνητική διαδικασία διεξάχθηκε βασισμένη στις επιταγές της επιστήμης της έρευνας του σχεδιασμού (DSR) και τα αποτελέσματα της έρευνας αυτής παρουσιάζονται ως αντικείμενο (artifact) της ίδιας μεθοδολογίας. Ειδικότερα, η ταξινόμηση δημιουργείται με την προσαρμογή του μοντέλου που πρότειναν οι Nickersson κ.α. (2013) στα δεδομένα της αγοράς των εφαρμογών της κινητής υγείας ακολουθώντας τις κατευθυντήριες γραμμές των συγγραφέων. Το αντικείμενο (το μοντέλο ταξινόμησης) αξιολογείται σε δύο φάσεις, κατά τη δημιουργία του και μετά την ολοκλήρωσή του. Η αξιολόγηση που λαμβάνει χώρα μετά την ολοκλήρωση του μοντέλου αφορά τη δοκιμή του σε αντιπροσωπευτικό δείγμα εφαρμογών για να επιβεβαιωθεί η χρησιμότητα του. Μετά το τέλος της δοκιμής του μοντέλου δημιουργείται και παρουσιάζεται μια περιγραφική θεωρία που εξηγεί τα πεδία, τις διαστάσεις και τις κατηγορίες που δημιουργήθηκαν ποιος είναι ο ρόλος τους στο οικοσύστημα και πως αλληλοεπιδρούν μεταξύ τους οι οντότητες. Η ανάπτυξη της θεωρίας βασίζεται και αυτή στην επιστήμη της έρευνας του σχεδιασμού και μεταφέρεται στον κλάδο των πληροφοριακών συστημάτων. Οι συνεισφορές αυτής της έρευνας είναι οι εξής: ένα σύστημα ταξινόμησης για τις εφαρμογές της κινητής υγείας και η ανάπτυξη θεωρίας γύρω από τη δομή και τις αλληλοσυσχετίσεις που δημιουργούνται στο συγκεκριμένο οικοσύστημα.
How Women Drove ‘Spirits’ out of Their Local Communities: The ‘Exorcism’ of Non-Governmental Organizations: A Comparative Case Study
Authors: Bogacz-Wojtanowska Ewa , Góral Anna , Wrona Sylwia
Published: December 2023

The process of system transformation in Poland and Central-Eastern Europe brought forth numerous economic benefits and social acceptance. However, it also presented challengingsocial problems, particularly at the local level. Non-governmental organizations (NGOs), often led by female leaders, took on the responsibility of gradually addressing these issues. By identifying the needs and expectations of the communities they served, NGOs became significant agents in resolving local social problems. Unfortunately, the actions andperspectives of women in these NGOs, who played a crucial role in their establishment and development over the decades of the system transformation period, remain inadequatelyrecognized in the existing literature. The research presented in this text aimed to explore and understand how women-led NGOs defined and addressed the social problems of localcommunities during the system transformation in Poland. To achieve this, the metaphor of spirits and exorcisms was employed. The research utilized a comparative case studyapproach, focusing on four NGOs founded and managed by women across different phases of the system transformation in Poland. In-depth interviews, observations, and documentand website analyses were conducted within each case study. This research contributes to the micro-level understanding of the contributions made by women-led NGOs to theprocess of system transformation in Poland.
Dual Bounds from Decision Diagram-Based Route Relaxations: An Application to Truck-Drone Routing
Authors: Tang Ziye , van Hoeve Willem-Jan
Published: December 2023

For vehicle routing problems, strong dual bounds on the optimal value are needed to develop scalable exact algorithms as well as to evaluate the performance of heuristics. In this work, we propose an iterative algorithm to compute dual bounds motivated by connections between decision diagrams and dynamic programming models used for pricing in branch-and-cut-and-price algorithms. We apply techniques from the decision diagram literature to generate and strengthen novel route relaxations for obtaining dual bounds without using column generation. Our approach is generic and can be applied to various vehicle routing problems in which corresponding dynamic programming models are available. We apply our framework to the traveling salesman with drone problem and show that it produces dual bounds competitive to those from the state of the art. Applied to larger problem instances in which the state-of-the-art approach does not scale, our method outperforms other bounding techniques from the literature.

Funding: This work was supported by the National Science Foundation [Grant 1918102] and the Office of Naval Research [Grants N00014-18-1-2129 and N00014-21-1-2240].

Supplemental Material: The online appendix is available at https://doi.org/10.1287/trsc.2021.0170 .
A EQUAÇÃO DE DRAKE E O PARADOXO DE FERMI: UMA ABORDAGEM DA ASTROBIOLOGIA
Authors: Silva Pinho Janildes , Alves Rodrigues Marli , Fernandes de Fernandes Iranderly
Published: December 2023

A busca por vida extraterrestre é um tema que desperta curiosidade há muito tempo e se constitui em um dos ramos de estudo da Astrobiologia. Astrobiologia é uma ciência recente, multidisciplinar que se ocupa em estudar desde a formação de moléculas orgânicas em ambientes atípicos até a compreensão dos mecanismos de manutenção da vida, tomando como base a origem e formação da vida na Terra. Esses estudos têm revelado grandes perspectivas da existência de vida não só no nosso Sistema Solar, mas também na Via Láctea e no Universo como um todo. Atualmente vivemos uma revolução tecnológica na área das explorações espaciais robóticas que tem contribuído com novas descobertas nesta área de pesquisa. Esse artigo se propõe a analisar a Equação de Drake, relacionando–a com o Paradoxo de Fermi contribuindo, assim, com mais uma ferramenta de discussão na Astrobiologia.
Validation of the Observer-Reported Communication Ability (ORCA) Measure for Individuals With Angelman Syndrome
Authors: Zigler Christina K. , Lin Li , McFatrich Molly , Lucas Nicole , Gordon Kelly L. , Jones Harrison N. , Berent Allyson , Panagoulias Jennifer , Evans Paula , Reeve Bryce B.
Published: December 2023

There is a critical need for high-quality clinical outcome assessments to capture the important aspects of communication ability of individuals with Angelman syndrome (AS). To center the perspective of caregivers, our team developed the novel Observer-Reported Communication Ability (ORCA) measure using best practice guidelines, with the goal of developing a measure that could be administered to caregivers directly without the need for a certified administrator for use in clinical trials. To refine the draft measure, we conducted two rounds of cognitive interviews with 24 caregivers and a quantitative study including 249 caregivers. The results from both studies support the overall content validity, construct validity, and the reliability of the ORCA measure for individuals with AS > 2 years old for use in research contexts. Future work should explore the responsiveness of ORCA measures to changes over time in a diverse sample.
Full field-of-view hexagonal lattice structured illumination microscopy based on the phase shift of electro–optic modulators
Authors: Ji Cheng , Zhu Yukun , He Enxing , Liu Qingqing , Zhou Dakai , Xie Shunyu , Wu Hanmeng , Zhang Jinfeng , Du Kuangwei , Chen Youhua , Liu Wenjie , Kuang Cuifang
Published: December 2023

High throughput has become an important research direction in the field of super-resolution (SR) microscopy, especially in improving the capability of dynamic observations. In this study, we present a hexagonal lattice structured illumination microscopy (hexSIM) system characterized by a large field of view (FOV), rapid imaging speed, and high power efficiency. Our approach employs spatial light interference to generate a two-dimensional hexagonal SIM pattern, and utilizes electro-optical modulators for high-speed phase shifting. This design enables the achievement of a 210-µm diameter SIM illumination FOV when using a 100×/1.49 objective lens, capturing 2048 × 2048 pixel images at an impressive 98 frames per second (fps) single frame rate. Notably, this method attains a near 100% full field-of-view and power efficiency, with the speed limited only by the camera's capabilities. Our hexSIM demonstrates a substantial 1.73-fold improvement in spatial resolution and necessitates only seven phase-shift images, thus enhancing the imaging speed compared to conventional 2D-SIM.
Topological charge identification of superimposed orbital angular momentum beams under turbulence using an attention mechanism
Authors: Zhang Yiwen , Zhao Wenqian , Xu Tianxu , Ren Yongxiong , Zhang Runzhou , Pan Zhongqi , Yue Yang
Published: December 2023

Due to the unique features, orbital angular momentum (OAM) beams have been widely explored for different applications. Accurate determination of the topological charge (TC) of these beams is crucial for their optimal utilization. In this paper, we propose a method that combines adaptive image processing techniques with a simple, parameter-free attention module (SimAM) based convolutional neural network to accurately identify the TC of high-order superimposed OAM beams. Experimental results demonstrate that under the combined influence of non-extreme light intensity and turbulence, it can achieve >95% identification accuracy of TCs ranging from ±1 to ±40. Moreover, even under partial-pattern-missing conditions, our method maintains an accuracy rate of over 80%. Compared with traditional attention mechanisms, SimAM does not require additional network design, significantly reducing the computational costs. Our approach showcases remarkable efficiency, robustness, and cost-effectiveness, making it adaptable to challenging factors such as non-uniform lighting and partially occluded light paths. This research provides a new direction for recognizing OAM modes with valuable implications for the future of communication systems.
Breaking the symmetric spiral spectrum distribution of a Laguerre-Gaussian beam propagating in moderate-to-strong isotropic atmospheric turbulence
Authors: Wu Dan , Wang Haiyun , Wang Fei , Wu Gaofeng , Zhu Xinlei , Cai Yangjian
Published: December 2023

We demonstrate that the spiral spectrum (also known as orbital angular momentum spectrum) of a Laguerre-Gaussian (LG) beam with topological charge (TC) l is asymmetrically broadened propagating through moderate-to-strong atmospheric turbulence, even the statistics of turbulence is isotropic. This phenomenon is quite different from that predicted in weak turbulence where the spiral spectrum of a disturbed LG beam is symmetric with respect to its TC number l. An explicit analytical expression of the spiral spectrum of the LG beam with l = 1 is derived based on the extend Huygens-Fresnel integral and quadratic approximation, which is used to illustrate the transition scenarios of the spiral spectrum from symmetry to asymmetry in weak-to-strong turbulence. The physical mechanism for the asymmetric spiral spectrum in moderate-to-strong turbulence is thoroughly discussed. Our results are confirmed by the multi-phase screen numerical simulations and are consistent with the experimental results reported in Phys. Rev. A 105, 053513 (2022)10.1103/PhysRevA.105.053513 and Opt. Lett. 38, 4062 (2013)10.1364/OL.38.004062.
Deep learning denoising diffusion probabilistic model applied to holographic data synthesis
Authors: Velez-Zea Alejandro , Gutierrez-Cespedes Cristian David , Barrera-Ramírez John Fredy
Published: December 2023

In this Letter, we demonstrate for the first time, to our knowledge, a holographic data synthesis based on a deep learning probabilistic diffusion model (DDPM). Several different datasets of color images corresponding to different types of objects are converted to complex-valued holographic data through backpropagation. Then, we train a DDPM using the resulting holographic datasets. The diffusion model is composed of a noise scheduler, which gradually adds Gaussian noise to each hologram in the dataset, and a U-Net convolutional neural network that is trained to reverse this process. Once the U-Net is trained, any number of holograms with similar features as those of the datasets can be generated just by inputting a Gaussian random noise to the model. We demonstrate the synthesis of holograms containing color images of 2D characters, vehicles, and 3D scenes with different characters at different propagation distances.
Using mixture density networks to emulate a stochastic within-host model of Francisella tularensis infection
Authors: Carruthers Jonathan , Finnie Thomas
Published: December 2023

For stochastic models with large numbers of states, analytical techniques are often impractical, and simulations time-consuming and computationally demanding. This limitation can hinder the practical implementation of such models. In this study, we demonstrate how neural networks can be used to develop emulators for two outputs of a stochastic within-host model of Francisella tularensis infection: the dose-dependent probability of illness and the incubation period. Once the emulators are constructed, we employ Markov Chain Monte Carlo sampling methods to parameterize the within-host model using records of human infection. This inference is only possible through the use of a mixture density network to emulate the incubation period, providing accurate approximations of the corresponding probability distribution. Notably, these estimates improve upon previous approaches that relied on bacterial counts from the lungs of macaques. Our findings reveal a 50% infectious dose of approximately 10 colony-forming units and we estimate that the incubation period can last for up to 11 days following low dose exposure.
How Merkel cells transduce mechanical stimuli: A biophysical model of Merkel cells
Authors: Mao Fangtao , Yang Wenzhen
Published: December 2023

Merkel cells combine with Aβ afferents, producing slowly adapting type 1(SA1) responses to mechanical stimuli. However, how Merkel cells transduce mechanical stimuli into neural signals to Aβ afferents is still unclear. Here we develop a biophysical model of Merkel cells for mechanical transduction by incorporating main ingredients such as Ca2+ and K+ voltage-gated channels, Piezo2 channels, internal Ca2+ stores, neurotransmitters release, and cell deformation. We first validate our model with several experiments. Then we reveal that Ca2+ and K+ channels on the plasma membrane shape the depolarization of membrane potentials, further regulating the Ca2+ transients in the cells. We also show that Ca2+ channels on the plasma membrane mainly inspire the Ca2+ transients, while internal Ca2+ stores mainly maintain the Ca2+ transients. Moreover, we show that though Piezo2 channels are rapidly adapting mechanical-sensitive channels, they are sufficient to inspire sustained Ca2+ transients in Merkel cells, which further induce the release of neurotransmitters for tens of seconds. Thus our work provides a model that captures the membrane potentials and Ca2+ transients features of Merkel cells and partly explains how Merkel cells transduce the mechanical stimuli by Piezo2 channels.
The effect of M. tuberculosis lineage on clinical phenotype
Authors: Du Duc Hong , Geskus Ronald B. , Zhao Yanlin , Codecasa Luigi Ruffo , Cirillo Daniela Maria , van Crevel Reinout , Pascapurnama Dyshelly Nurkartika , Chaidir Lidya , Niemann Stefan , Diel Roland , Omar Shaheed Vally , Grandjean Louis , Rokadiya Sakib , Ortitz Arturo Torres , Lân Nguyễn Hữu , Hà Đặng Thị Minh , Smith E. Grace , Robinson Esther , Dedicoat Martin , Nhat Le Thanh Hoang , Thwaites Guy E. , Van Le Hong , Thuong Nguyen Thuy Thuong , Walker Timothy M.
Published: December 2023

Six lineages of Mycobacterium tuberculosis sensu stricto (which excludes M. africanum) are described. Single-country or small observational data suggest differences in clinical phenotype between lineages. We present strain lineage and clinical phenotype data from 12,246 patients from 3 low-incidence and 5 high-incidence countries. We used multivariable logistic regression to explore the effect of lineage on site of disease and on cavities on chest radiography, given pulmonary TB; multivariable multinomial logistic regression to investigate types of extra-pulmonary TB, given lineage; and accelerated failure time and Cox proportional-hazards models to explore the effect of lineage on time to smear and culture-conversion. Mediation analyses quantified the direct effects of lineage on outcomes. Pulmonary disease was more likely among patients with lineage(L) 2, L3 or L4, than L1 (adjusted odds ratio (aOR) 1.79, (95% confidence interval 1.49–2.15), p<0.001; aOR = 1.40(1.09–1.79), p = 0.007; aOR = 2.04(1.65–2.53), p<0.001, respectively). Among patients with pulmonary TB, those with L1 had greater risk of cavities on chest radiography versus those with L2 (aOR = 0.69(0.57–0.83), p<0.001) and L4 strains (aOR = 0.73(0.59–0.90), p = 0.002). L1 strains were more likely to cause osteomyelitis among patients with extra-pulmonary TB, versus L2-4 (p = 0.033, p = 0.008 and p = 0.049 respectively). Patients with L1 strains showed shorter time-to-sputum smear conversion than for L2. Causal mediation analysis showed the effect of lineage in each case was largely direct. The pattern of clinical phenotypes seen with L1 strains differed from modern lineages (L2-4). This has implications for clinical management and could influence clinical trial selection strategies.
Developing a diversity, equity and inclusion compass to guide scientific capacity strengthening efforts in Africa
Authors: Kasprowicz Victoria O. , Waddilove Kim Darley , Chopera Denis , Khumalo Sipho , Harilall Sashin , Wong Emily B. , Karita Etienne , Sanders Eduard J. , Kilembe William , Gaseitsiwe Simani , Ndung’u Thumbi
Published: December 2023

Diversity, equity and inclusion (DEI) in science is vital to improve the scientific process and ensure societal uptake and application of scientific results. DEI challenges include a full spectrum of issues from the lack of, and promotion of, women in science, to the numerous barriers in place that limit representation of African scientists in global scientific efforts. DEI principles in African science remain relatively underdeveloped, with limited engagement and discussion among all stakeholders to ensure that initiatives are relevant to local environments. The Sub-Saharan African Network for TB/HIV research Excellence (SANTHE) is a network of African-led research in HIV, tuberculosis (TB), associated co-morbidities, and emerging pathogens, now based in eight African countries. Our aim, as a scientific capacity strengthening network, was to collaboratively produce a set of DEI guidelines and to represent them visually as a DEI compass. We implemented a consortium-wide survey, focus group discussions and a workshop where we were able to identify the key DEI challenges as viewed by scientists and support staff within the SANTHE network. Three thematic areas were identified: 1. Conquering Biases, 2. Respecting the Needs of a Diverse Workforce (including mental health challenges, physical disability, career stability issues, demands of parenthood, and female-specific challenges), and 3. Promotion of African Science. From this we constructed a compass that included proposed steps to start addressing these issues. The use of the compass metaphor allows ‘re-adjustment/re-positioning’ making this a dynamic output. The compass can become a tool to establish an institution’s DEI priorities and then to progress towards them.