bluuebunny/crossref_metadata_2025 huggingface dataset:
Introduction to Development Engineering
Authors: Agnihotri Anustubh , Madon Temina , Gadgil Ashok J.
Published: September 2022

Technological change has always played a role in shaping human progress. From the power loom to the mobile phone, new technologies have continuously influenced how social and economic activities are organized—sometimes for better and sometimes for worse. Agricultural technologies, for example, have increased the efficiency of agricultural production and catalyzed the restructuring of economies (Bustos et al., 2016). At the same time, these innovations have degraded the environment and, in some cases, fueled inequality (Foster and Rosenzweig, 2008; Pingali, 2012). Information technology has played a catalytic role in social development, enabling collective action and inclusive political movements (Enikolopov et al., 2020; Manacorda & Tesei, 2020); yet it has also fueled political violence and perhaps even genocide (Pierskalla & Hollenbach, 2013; Fink, 2018).
Customised E-Learning Platforms
Authors: Pitchford Nicola
Published: September 2022

More than 617 million children and adolescents lack the basic reading and mathematics skills required to live healthy and productive lives. Malawi ranks particularly poorly, with an average pupil to teacher ratio of 77:1 and a 50% dropout rate among primary school children. Established in 2013, the Unlocking Talent initiative uses e-Learning technology to help overcome educational challenges. It equips touch-screen tablets with customisable software that delivers lessons through multisensory experiences (e.g. pictures, sound, video and animation). Throughout Malawi, small groups of students in public primary schools have accessed these tablets during weekly sessions on-site. This case study describes a series of evaluations of this e-Learning technology in Malawi, conducted in tandem with experiments in other countries (including the United Kingdom, Brazil, South Africa, Tanzania, Kenya and Ethiopia). Following a pilot evaluation to assess the feasibility of e-Learning in raising learning outcomes, multiple large-scale randomised control trials were conducted. Learning gains hold across multiple cohorts of children and across different countries, generating more than a 3-month advantage in basic mathematics and more than a 4-month advantage in basic reading on average. The intervention also bridges gender gaps in mathematics skills attainment in Malawi.
Digital Networking and the Case of Youth Unemployment in South Africa
Authors: Shaw Patrick , Wheeler Laurel
Published: September 2022

South Africa has one of the highest rates of youth unemployment and under-employment around the world, despite having a relatively large formal sector. This is driven, in part, by frictions in labor markets, including lack of information about job applicants’ skills, limited access to job training, and employers’ reliance on referrals through professional networks for hiring. This case study explores whether the online platform LinkedIn can be used to improve the employment outcomes of disadvantaged youth in South Africa. Researchers worked with an NGO, the Harambee Youth Employment Accelerator, to develop a training for young workseekers in the use of LinkedIn for job search, applications, and networking for referrals. This intervention was randomized across 30 cohorts of youth, with more than 1600 students enrolled in the study. The research team worked with LinkedIn engineers to access data generated by the platform. The evaluation finds that participants exposed to the LinkedIn training (the “treated” participants) were 10% more likely than the control group to find immediate employment, an effect that persisted for at least a year after job readiness training.
Amplifying Worker Voice with Technology and Organizational Incentives
Authors: Adhvaryu Achyuta , Gade Smit , Gandhi Piyush , Garg Lavanya , Kabra Mansi , Nanda Ankita , Nyshadham Anant , Patil Arvind , Pimoli Mamta
Published: September 2022

Economic development can be driven by large, high-performing firms that provide safe, dignified jobs with living wages. The garment manufacturing industry is a large, economically important sector concentrated in low- and middle-income countries; however, it has been characterized by persistent neglect of workers’ concerns and working conditions. This case study explores whether digital communication platforms, combined with improvements in management, can empower garment factory workers to voice their concerns and have their grievances addressed. We describe a series of randomized experiments testing the effectiveness of different grievance reporting solutions, finding that access to an anonymous complaint service improves worker satisfaction and reduces absenteeism. However, these simple solutions do not adequately address issues around management trust, accountability, and quality. An ongoing experiment explores whether grievance reporting technology, combined with team-based performance incentives for management, can further improve outcomes for workers.
Stopping Arsenic Poisoning in India
Authors: Gadgil Ashok J. , Amrose Susan , Hernandez Dana
Published: September 2022

In the 1980s, most households of rural India and Bangladesh switched from surface sources for their drinking water – which was causing high incidence of diarrheal disease – to groundwater extracted by hand pumps. However, for tens of millions of people, this groundwater contained high levels of arsenic, which has led to what the WHO has called the “largest mass poisoning of a population in history.” This case study describes the development of ElectroChemical Arsenic Remediation (ECAR), which is a technology that uses iron electrodes to oxidize and remove aqueous arsenic from drinking water. Pilot evaluation of ECAR began in 2011, with a 100 L reactor at a school in Amirabad. However, political tensions in Amirabad caused the subsequent 600 L reactor pilot to be relocated to a school in Dhapdhapi. The findings from this pilot enabled the construction of a 10,000-liter per day (LPD) ECAR plant at Dhapdhapi. During this scaling up process, technical and contextual challenges were encountered and overcome, including those arising from intermittent power supply and a hot/humid climate. Additionally, implementation challenges included training of local operators, ensuring continuity of knowledge within the team, revisiting and correcting early mistakes, and additional engineering work needed during commissioning. The 10,000 LPD plant has been successful both technically and financially. However, after the handoff of the ECAR technology and plant to the local partner, Livpure in 2016, no widespread replication of ECAR plants in the region has occurred. The engineering science behind ECAR continues to be an active area of research, with ongoing projects investigating the implementation of next-generation ECAR technologies in rural California and the Philippines.
Sensing Change: Measuring Cookstove Adoption with Internet-of-Things Sensors
Authors: Wilson Daniel L.
Published: September 2022

By 2012, the civil war in Darfur, Sudan, had been ongoing for 9 years. The war had displaced missions of people and concentrated them into camps for internally-displaced people. This put immense strain on the local availability of woody biomass used for cooking. Women are primarily responsible for collecting fuelwood, and it was estimated that a 7-hour round trip was necessary to collect sufficient firewood for 2 or 3 days, causing great physical hardship to the women and exposing them to extreme risk of sexual violence as they ventured outside the safety of the camps. The Berkeley-Darfur Stove had been demonstrated to reduce fuel use by roughly 50%. However, recall error and social-desirability bias makes evaluating stove use through surveys challenging. This case study chronicles the integration of low-cost temperature sensors into the Berkeley-Darfur Stove to measure actual use (in contrast to self-reported use), as well as the challenges associated with conducting fieldwork and processing large datasets. Based on this work, it was determined that at least 75% of the women who received the Berkeley-Darfur Stove for free actually adopted it for routine use. Additionally, it was (serendipitously) found that just the act of conducting follow-up surveys had a significant positive impact on adoption. In-person surveys were also conducted, and no correlation was found between the stated use frequency of the cookstoves and the measured use frequency (as determined by the sensors), likely due to the social-desirability bias. This work has launched a variety of ventures including the development of data processing software, improved sensor design, and—most recently—the founding of Geocene, a company focused on expanding the application of remote sensors and providing consulting for companies building Internet of Things (IoT) products.
Reimagining Excreta as a Resource: Recovering Nitrogen from Urine in Nairobi, Kenya
Authors: Tarpeh William A. , Clark Brandon D. , Nelson Kara L. , Orner Kevin D.
Published: September 2022

Only 10–15% of Nairobi’s informal settlements are sewered, and these sewer pipes are often broken or clogged. In addition to posing a threat to human health, human waste contains high concentrations of nitrogen and phosphorus, which can wreak ecological harm when improperly discharged. However, nitrogen and phosphorus are also key ingredients for fertilizers used in agricultural food production. This case study follows the development of ElectroSan, a pre-revenue process engineering spinoff that focuses on novel processes for converting urine into valuable products. The two primary technologies ElectroSan uses to extract nitrogen from urine are ion exchange and electrochemical stripping. The efficacy of these technologies (primarily ion exchange) was investigated through field trials enabled by a partnership with Sanergy in Nairobi, Kenya. Through experimentation and market analyses, Dowex Mac 3 was identified as the most suitable resin for nitrogen recovery. Additionally, this process could produce ammonium sulfate fertilizer at a lower cost to competing products and also had the advantages of providing a steady, local supply of fertilizer that could be applied by fertigation. This approach thus avoided local ecosystem damage from improper disposal, created local economic opportunities, and partially closed the nutrient cycle locally. Life cycle and techno-economic assessments (in the context of San Francisco, CA) found that the sulfuric acid used for regeneration of the resin represented 70% of greenhouse gas emissions and energy input (embedded energy from the manufacturing process). Providing insights into the importance of partnerships, being adaptive with assumptions, and the realities of conducting fieldwork, the ElectroSan research project continues to explore the valorization of urine and has expanded to new contexts, including other parts of Kenya (with Sanivation) and Dakar, Senegal (with Delvic Sanitation Initiatives).
Engineering Predictable Water Supply: The Humans Behind the Tech
Authors: Hyun Christopher , Kumar Tanu , Post Alison E. , Ray Isha
Published: September 2022

Although it was reported in 2012 that 89% of the world’s population had access to piped water, it is estimated that at least one billion people receive this water for fewer than 24 h per day. Intermittency places a variety of burdens upon households, including inadequate quantities of supply at the household level, unpredictability of water utilities in making water available, and a disproportionate time burden on poorer households. For many intermittent water systems, the availability of water is controlled by valvemen who turn access on/off to various portions of their service area. Using this information, NextDrop sends notifications via mobile phones to customers as to when water is likely to be available. Although a pilot of NextDrop was successfully implemented in Hubli-Dharwad in India, NextDrop faced significant challenges when expanding to Bangalore. This case study investigates how a breakdown in the information pipeline, as well as corresponding human factors, prevented adoption of NextDrop in Bangalore. Specifically, randomized controlled trials found that valvemen sent reports of their activities to NextDrop only 70% of the time. Even when NextDrop passed messages onto customers, only 38% of customers reported receiving notifications, primarily because either the household “waiters” for water, usually women, did not have daytime access to the mobile phone registered with NextDrop or the notifications are buried under the many other solicitations and informational messages regularly received via SMS. Valvemen were further studied through observation and semi-structured interviews to understand their incentives for complying with NextDrop.
Technology and Development
Authors: Bishop Menna , Burgess Robin , Zipfel Céline
Published: September 2022

Two major challenges face humanity in the coming century. The first is to generate the innovations and productivity improvements that will keep people on a path to higher standards of living. The second is to ensure that expanding human activity does not generate negative environmental externalities that block this path to progress. In short, our future is about balancing the need for growth with the externalities that arise from that growth.
Connecting Communities Through Mobile Networks: A Case Study of Implementing Community Cellular Networks in the Philippines
Authors: Barela Mary Claire , Cunanan Maria Theresa , Festin Cedric Angelo , Heimerl Kurtis , Jang Esther , Johnson Matthew William , Martinez Philip , Vistal Ronel Vincent
Published: September 2022

Community networking can provide telecommunications in unserved and underserved areas where markets fail to deliver adequate Internet service due to high risk of investment and limited returns. This has left an estimated 400 million people worldwide in areas uncovered by mobile networks. In much of the Philippines, with just under 70% mobile phone penetration, unserved communities have limited connectivity options. We describe the CoCoMoNets (Connecting Communities through Mobile Networks) project implemented by the University of the Philippines Diliman (UPD) and international researchers, which delivered basic mobile telephony to remote rural barangays through community cellular networks. The core technology is a low-power, low-cost GSM base station operating at a fraction of the capital and recurring costs of traditional equipment. Deploying Filipino community networks presented unique challenges requiring extensive stakeholder coordination, including an MNO, regulators, local governments, local cooperatives, and end users. The project team encountered challenges including spectrum sharing, tower licensing, geographical remoteness, maintenance difficulties, local politics, and community relations. This chapter documents the project’s experiences and challenges in testing the community cellular model in the real world. After 2 years of operation, the researchers summarize their learnings to contribute to the development of future approaches in delivering sustainable last-mile communication access.
A Practical Framework for Research
Authors: Madon Temina , Agnihotri Anustubh , Gadgil Ashok J.
Published: September 2022

This chapter outlines a practical framework for designing scalable technology solutions that solve development challenges. We begin with an overview of the common constraints to sustainable development that often are encountered in the context of poverty. These constraints are based on a large body of research in development economics, political economy, psychology, and other social sciences; and they help to explain why engineering innovations so frequently fail to achieve outcomes when implemented in the real world. In the second part of this chapter, we provide a framework for implementing development engineering projects, consisting of four key activities: innovation, implementation, evaluation, and adaptation. Combining these activities in an iterative (and usually nonlinear) path allows the researcher to anticipate and design around the most common pitfalls associated with “technology for development.”
Monitoring Industrial Pollution in India
Authors: Sudarshan Anant
Published: September 2022

Many developing countries are attempting to prevent a rapid deterioration of air quality while still encouraging economic growth. In settings where state capacity is severely limited, enhancing the effectiveness of regulators is critical to success. Previous work has documented how Indian environmental regulators are constrained by having poor information on the pollution emitted by manufacturing plants, due to high monitoring costs, corruption, or staff constraints. This case study discusses a pilot project in the Indian state of Gujarat, designed to evaluate the benefits of Continuous Emissions Monitoring Systems (CEMS) – technology used to remotely monitor pollution emitted by industrial plants in real time. We show how the institutional context in which CEMS was deployed, which included an inflexible legal and regulatory framework and collusion between industry and labs to falsify data, cannot be divorced from an assessment of the performance of the technology solution. The eventual benefits of CEMS in the status quo regulatory framework proved limited. Nevertheless, the technology also provided an opportunity to change the rules of the game, allowing Gujarat to experiment with India’s first emissions trading scheme.
Data Space Best Practices for Data Interoperability in FinTechs
Authors: Serrano Martín , Curry Edward , Walsh Richards , Purtill Gavin , Soldatos John , Ferraris Maurizio , Troiano Ernesto
Published: September 2022

This chapter focuses on data interoperability best practices related to semantic technologies and data management systems. It introduces a particular view on how relevant data interoperability is achieved and its effects on developing technologies for the financial and insurance sectors. Financial technology (FinTech) and insurance technology (InsuranceTech) are rapidly developing and have created new business models and transformed the financial and insurance services industry in the last few years. The transformation is ongoing, and like many other domains, the vast amount of information available today known as Big Data, the data generated by IoT, and AI applications and also the technologies for data interoperability, which allows data nowadays to be reused, shared, and exchange, will have a strong influence. It is evident the entire financial sector is in a moment of new opportunities with a new vision for substantial growth. This book chapter analyzes the basis of data space design and discusses the best practices for data interoperability by introducing concepts and illustrating the way to understand how to enable the interoperability of information using a methodological approach to formalize and represent financial data by using semantic technologies and information models (knowledge engineering). This chapter provides a state-of-the-art offer called INFINITECH Way using the discussed best practices and explains how semantics for data interoperability are introduced as part of the FinTechs and InsuranceTech.
A Digital Twin Platform for Industrie 4.0
Authors: Redeker Magnus , Weskamp Jan Nicolas , Rössl Bastian , Pethig Florian
Published: September 2022

In an Industrie 4.0 (I4.0), rigid structures and architectures applied in manufacturing and industrial information technologies today will be replaced by highly dynamic and self-organizing networks. Today’s proprietary technical systems lead to strictly defined engineering processes and value chains. Interacting Digital Twins (DTs) are considered an enabling technology that could help increase flexibility based on semantically enriched information. Nevertheless, for interacting DTs to become a reality, their implementation should be based on open standards for information modeling and application programming interfaces like the Asset Administration Shell (AAS). Additionally, DT platforms could accelerate development and deployment of DTs and ensure their resilient operation.

This chapter develops a suitable architecture for such a DT platform for I4.0 based on user stories, requirements, and a time series messaging experiment. An architecture based on microservices patterns is identified as the best fit. As an additional result, time series data should not be integrated synchronously and directly into AASs, but rather asynchronously, either via streams or time series databases. The developed DT platform for I4.0 is composed of specialized, independent, loosely coupled microservices interacting use case specifically either syn- or asynchronously. It can be structured into four layers: continuous deployment, shop-floor, data infrastructure, and business services layer. An evaluation is carried out based on the DT controlled manufacturing scenario: AAS-based DTs of products and manufacturing resources organize manufacturing by forming highly dynamic and self-organizing networks.

Future work should focus on a final, complete AAS integration into the data infrastructure layer, just like it is already implemented on the shop-floor and business services layers. Since with the standardized AAS only one interface type would then be left in the DT platform for I4.0, DT interaction, adaptability, and autonomy could be improved even further. In order to become part of an I4.0 data space, the DT platform for I4.0 should support global discovery, data sovereignty, compliance, identity, and trust. For this purpose, Gaia-X Federation Services should be implemented, e.g., as cross-company connectors.
Coronoidaufbau mittels Beckenkammspan über einen medialen Zugang zur Therapie von chronischen Coronoiddefekten mit posteromedialer Rotationsinstabilität
Authors: Schneider M. M. , Zimmermann F. , Hollinger B. , Zimmerer A. , Burkhart K. J.
Published: September 2022

Operationsziel

Ziel ist die Wiederherstellung der ulnohumeralen Gelenkkongruenz mit Neutralisierung der posteromedialen Instabilität (PMRI) und der damit einhergehenden chronischen Fehlstellung des Ellenbogens.

Indikationen

Neben akuten Defekten, auf die im Artikel nicht näher eingegangen werden soll, besteht die Indikation zum Coronoidaufbau bei chronischen Defekten der anteromedialen Facette des Coronoids mit PMRI.

Kontraindikationen

Gegen die Durchführung der Operation sprechen fortgeschrittene Knorpelschäden des Ellenbogens sowie allgemeine Kontraindikationen (akuter Infekt, Schwangerschaft, fehlende Operabilität des Patienten etc.)

Operationstechnik

Über einen medialen Zugang wird zunächst das Coronoidbett präpariert. Im Anschluss wird ein autologer Beckenkammspan auf den Defekt aufgebracht, an die Gelenkfläche anpasst und mittels Schrauben- oder Plattenosteosynthese dauerhaft fixiert. Additiv wird eine Rekonstruktion des anterioren Bündels des medialen Kollateralbandes durchgeführt und die Kapsel bzw. Flexoren werden zum Ende der Operation verschlossen respektive rekonstruiert.

Weiterbehandlung

Postoperativ wird eine Bewegungsorthese angepasst, die für 6 Wochen getragen werden sollte. Der Ellenbogen kann unmittelbar nach Operation schmerzadaptiert frei funktionell beübt werden. Die Therapie wird durch einen CPM-Ellenbogenstuhl unterstützt.

Ergebnisse

Zwischen 04/2015 und 11/2017 wurden 10 Patienten mit chronischen Coronoiddefekten mit dieser Technik operiert. Acht der 10 Patienten standen 86 Wochen postoperativ für ein Follow-up zur Verfügung. Die durchschnittlich 41,4 Jahre alten Patienten wiesen postoperativ alle einen gesteigerten Bewegungsumfang, regelrechte radiologische Stellungskontrollen ohne Subluxationen und Verbesserungen in Funktionsscores auf. Ein Patient wurde ausgeschlossen, weil eine Konversion in eine Ellenbogenprothese notwendig wurde. Mit der beschriebenen Technik ließ sich eine objektive wie subjektive Verbesserung der chronischen PMRI erreichen.
Deep inspiration breath-hold radiation therapy in left-sided breast cancer patients: a single-institution retrospective dosimetric analysis of organs at risk doses
Authors: Wolf Jule , Stoller Sabine , Lübke Jördis , Rothe Thomas , Serpa Marco , Scholber Jutta , Zamboglou Constantinos , Gkika Eleni , Baltas Dimos , Juhasz-Böss Ingolf , Verma Vivek , Krug David , Grosu Anca-Ligia , Nicolay Nils H. , Sprave Tanja
Published: September 2022

Background

Radiotherapy can induce cardiac injury in left-sided breast cancer cases. Cardiac-sparing irradiation using the deep inspiration breath-hold (DIBH) technique can achieve substantial dose reduction to vulnerable cardiac substructures compared with free breathing (FB). This study evaluated the dosimetric differences between both techniques at a single institution.

Methods

From 2017 to 2019, 130 patients with left-sided breast cancer underwent breast-conserving surgery (BCS; n = 121, 93.1%) or mastectomy (ME; n = 9, 6.9%) along with axillary lymph node staging (n = 105, 80.8%), followed by adjuvant irradiation in DIBH technique; adjuvant systemic therapy was included if applicable. 106 (81.5%) patients received conventional and 24 (18.5%) hypofractionated irradiation. Additionally, 12 patients received regional nodal irradiation. Computed tomography (CT) scans in FB and DIBH position were performed for all patients. Intrafractional 3D position monitoring of the patient surface in deep inspiration and breath gating was performed using Sentinel and Catalyst HD 3D surface scanning systems (C-RAD, Catalyst, C‑RAD AB, Uppsala, Sweden). Individual coaching and determination of breathing amplitude during the radiation planning CT was performed. Three-dimensional treatment planning was performed using standard tangential treatment portals (6 or 18 MV). The delineation of cardiac structures and both lungs was done in both the FB and the DIBH scan.

Results

All dosimetric parameters for cardiac structures were significantly reduced (p < 0.01 for all). The mean heart dose (Dmean) in the DIBH group was 1.3 Gy (range 0.5–3.6) vs. 2.2 Gy (range 0.9–8.8) in the FB group (p < 0.001). The Dmean for the left ventricle (LV) in DIBH was 1.5 Gy (range 0.6–4.5), as compared to 2.8 Gy (1.1–9.5) with FB (p < 0.001). The parameters for LV (V10 Gy, V15 Gy, V20 Gy, V23 Gy, V25 Gy, V30 Gy) were reduced by about 100% (p < 0.001). The LAD Dmean in the DIBH group was 4.1 Gy (range 1.2–33.3) and 14.3 Gy (range 2.4–37.5) in the FB group (p < 0.001). The median values for LAD such as V15 Gy, V20 Gy, V25 Gy, V30 Gy, and V40 Gy decreased by roughly 100% (p < 0.001). An increasing volume of left lung in the DIBH position resulted in dose sparing of cardiac structures.

Conclusion

For all ascertained dosimetric parameters, a significant dose reduction could be achieved in DIBH technique.
Neue S3-Leitlinie Prostatakarzinom 2021 (Version 6.2) – Was hat sich beim fortgeschrittenen Prostatakarzinom geändert?
Authors: Thomas C. , Schrader A. J.
Published: September 2022

Zur Therapie des metastasierten hormonsensitiven oder kastrationsresistenten Prostatakarzinoms (mHSPC, mCRPC) gab es in den letzten Jahren zahlreiche neue Erkenntnisse aus klinischen Studien. Die neu zugelassenen Behandlungsoptionen machen die Therapieplanung und Therapiesequenz anspruchsvoller. Hinzu kommt, dass die Lokaltherapie des metastasierten Prostatakarzinoms zunehmend an Bedeutung gewinnt. Im neuen Update 6.2 der S3-Leitlinie zum Prostatakarzinom vom Oktober 2021 wurden die neuen Entwicklungen bei den Empfehlungen zur Behandlung des mHSPC und mCRPC umgesetzt, deren wichtigsten Neuerungen und die daraus resultierenden Empfehlungen für die Praxis dargestellt werden.
Functional biomarkers derived from computed tomography and magnetic resonance imaging differentiate PDAC subgroups and reveal gemcitabine-induced hypo-vascularization
Authors: Heid Irina , Trajkovic-Arsic Marija , Lohöfer Fabian , Kaissis Georgios , Harder Felix N. , Mayer Moritz , Topping Geoffrey J. , Jungmann Friderike , Crone Barbara , Wildgruber Moritz , Karst Uwe , Liotta Lucia , Algül Hana , Yen Hsi-Yu , Steiger Katja , Weichert Wilko , Siveke Jens T. , Makowski Marcus R. , Braren Rickmer F.
Published: September 2022

Purpose

Pancreatic ductal adenocarcinoma (PDAC) is a molecularly heterogeneous tumor entity with no clinically established imaging biomarkers. We hypothesize that tumor morphology and physiology, including vascularity and perfusion, show variations that can be detected by differences in contrast agent (CA) accumulation measured non-invasively. This work seeks to establish imaging biomarkers for tumor stratification and therapy response monitoring in PDAC, based on this hypothesis.

Methods and materials

Regional CA accumulation in PDAC was correlated with tumor vascularization, stroma content, and tumor cellularity in murine and human subjects. Changes in CA distribution in response to gemcitabine (GEM) were monitored longitudinally with computed tomography (CT) Hounsfield Units ratio (HUr) of tumor to the aorta or with magnetic resonance imaging (MRI) ΔR1 area under the curve at 60 s tumor-to-muscle ratio (AUC60r). Tissue analyses were performed on co-registered samples, including endothelial cell proliferation and cisplatin tissue deposition as a surrogate of chemotherapy delivery.

Results

Tumor cell poor, stroma-rich regions exhibited high CA accumulation both in human (meanHUr 0.64 vs. 0.34, p < 0.001) and mouse PDAC (meanAUC60r 2.0 vs. 1.1, p < 0.001). Compared to the baseline, in vivo CA accumulation decreased specifically in response to GEM treatment in a subset of human (HUr −18%) and mouse (AUC60r −36%) tumors. Ex vivo analyses of mPDAC showed reduced cisplatin delivery (GEM: 0.92 ± 0.5 mg/g, vs. vehicle: 3.1 ± 1.5 mg/g, p = 0.004) and diminished endothelial cell proliferation (GEM: 22.3% vs. vehicle: 30.9%, p = 0.002) upon GEM administration.

Conclusion

In PDAC, CA accumulation, which is related to tumor vascularization and perfusion, inversely correlates with tumor cellularity. The standard of care GEM treatment results in decreased CA accumulation, which impedes drug delivery. Further investigation is warranted into potentially detrimental effects of GEM in combinatorial therapy regimens.
Five-year results after total knee arthroplasty in lymphoedema and lipoedema: encouraging functional and clinical outcomes and low rates of infection
Authors: Granger Luke , Bolam Scott M. , Sur Avtar , Mitchell Philip , Hutt Jonathan , Sandiford Nemandra A.
Published: September 2022

Background

The aim of this study was to define outcomes after total knee arthroplasty (TKA) in lymphoedema and lipoedema patients managed by a multidisciplinary team and daily compression bandaging.

Methods

A retrospective study was performed in a single centre. Between 2007 and 2018, 36 TKA procedures were performed on 28 consecutive patients with a diagnosis of lymphoedema and lipoedema. Oxford Knee Scores (OKS), EuroQol-5D (EQ-5D) scores, satisfaction scores, radiographs, and complications were obtained at the final follow-up. Patients were admitted to the hospital up to two weeks prior to surgery and remained on the ward for daily compression bandaging by the specialist lymphoedema team.

Results

Over the study period, 36 TKAs were performed on 28 patients (5 males, 23 females) with a mean age of 71 years (range 54–90). Of these, 30 TKAs were in patients with lymphoedema, five with lipoedema, and one with a dual diagnosis. Overall, 28 TKAs (21 patients) were available at the final follow-up with a mean follow-up time of 61 months (range 9–138). The mean BMI was 38.5 kg/m2. The mean pre-operative and post-operative Oxford Knee Score increased from 18 (range 2–38) to 29 (range 10–54); p < 0.001. EQ-5D score increased from 0.48 (range 0.15–0.80) to 0.74 (0.34–1.00) (p < 0.001). Mean post-operative satisfaction was 7.6/10 (range 2–10), with 89.3% TKAs satisfied. Complications were one (4%, 1/28) deep vein thrombosis, one superficial wound infection, one prosthetic joint infection, one stiff knee requiring manipulation, and one intra-operative femoral fracture.

Conclusions

Lymphoedema and lipoedema should not be seen as barriers to TKA if adopting a multidisciplinary approach.
SVF-GEL Cryopreserved for Different Times Exhibits Varied Preservation and Regeneration Potential After Transplantation in a Mouse Model
Authors: Tao Yue , Zhao Zheng-Nan , Xiang Xin-Jian , Liang Ze-Xu , Zhao Yu
Published: September 2022

Background

Matrix vascular component (SVF) gels derived from fat preserve tissue integrity and cell viability under cryopreserved conditions, making them easy to inject again for later use. Here, we compared the preservation power and regeneration potential of SVF-gel under different cryopreservation times.

Methods

The SVF-gel stored under − 20 °C, without cryoprotectant cryopreservation for 5, 15, and 45 days, with fresh SVF-gel as control. We evaluated the rate of volume retention after thawing the SVF-gel and the apoptosis rate of adipose-derived stem cells. Next, we analyzed retention rated, adipogenesis, angiogenesis, and connective tissue hyperplasia of the grafts, one month after subcutaneously transplanting the specimen into immunodeficient mice.

Results

SVF-gel cryopreserved for 5 and 15 days exhibited no significant different in apoptosis rates relative to the control group. Extending the cryopreservation time to 45 days resulted in significantly increased and decreased apoptosis and volume retention rates of SVF-gel, respectively. SVF-gel grafts cryopreserved for 5 and 15 days exhibited no significant differences from those in the control group, although their weights and volumes still fluctuated. Extending the cryopreservation time to 45 days resulted in significantly decreased retention rates of the grafts. Histologically, extending freezing time resulted in a gradual decline in the graft’s health adipose tissue, as well as decreased angiogenesis, and connective tissue hyperplasia.

Conclusion

Simple freezing of SVF-gel at − 20 °C conferred them with sufficient cell viability. Notably, short-term cryopreservation did not significantly increase the apoptosis rate, and it still had a certain regeneration after transplantation. However, prolonging freezing time to 45 days resulted in increased apoptosis rate and worsened transplantation effect.

No Level Assigned

This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Circulating tumor DNA in Hodgkin lymphoma
Authors: Maco Maria , Kupcova Kristyna , Herman Vaclav , Ondeckova Iva , Kozak Tomas , Mocikova Heidi , Havranek Ondrej ,   On behalf of the Czech Hodgkin Lymphoma Study Group
Published: September 2022

Somatic mutations of genes involved in NF-κB, PI3K/AKT, NOTCH, and JAK/STAT signaling pathways play an important role in the pathogenesis of Hodgkin lymphoma (HL). HL tumor cells form only about 5% of the tumor mass; however, it was shown that HL tumor-derived DNA could be detected in the bloodstream. This circulating tumor DNA (ctDNA) reflects the genetic profile of HL tumor cells and can be used for qualitative and quantitative analysis of tumor-specific somatic DNA mutations within the concept of liquid biopsy. Overall, the most frequently mutated gene in HL is STAT6; however, the exact spectrum of mutations differs between individual HL histological subtypes. Importantly, reduction of ctDNA plasma levels after initial treatment is highly correlated with prognosis. Therefore, ctDNA shows great promise as a novel tool for non-invasive tumor genome analysis for biomarker driven therapy as well as for superior minimal residual disease monitoring and treatment resistance detection. Here, we summarize the recent advancements of ctDNA analysis in HL with focus on ctDNA detection methodologies, genetic profiling of HL and its clonal evolution, and the emerging prognostic value of ctDNA.
Heterogeneities among credit risk parameter distributions: the modality defines the best estimation method
Authors: Gürtler Marc , Zöllner Marvin
Published: September 2022

Comparative studies investigating the estimation accuracy of statistical methods often arrive at different conclusions. Therefore, it remains unclear which method is best suited for a particular estimation task. While this problem exists in many areas of predictive analytics, it has particular relevance in the banking sector owing to regulatory requirements regarding transparency and quality of estimation methods. For the estimation of the relevant credit risk parameter loss given default (LGD), we find that the different results can be attributed to the modality type of the respective LGD distribution. Specifically, we use cluster analysis to identify heterogeneities among the LGD distributions of loan portfolios of 16 European countries with 32,851 defaulted loans. The analysis leads to three clusters, whose distributions essentially differ in their modality type. For each modality type, we empirically determine the accuracy of 20 estimation methods, including traditional regression and advanced machine learning. We show that the specific modality type is crucial for the best method. The results are not limited to the banking sector, because the present distribution type-dependent recommendation for method selection, which is based on cluster analysis, can also be applied to parameter estimation problems in all areas of predictive analytics.
Visual ensemble selection of deep convolutional neural networks for 3D segmentation of breast tumors on dynamic contrast enhanced MRI
Authors: Rahimpour Masoomeh , Saint Martin Marie-Judith , Frouin Frédérique , Akl Pia , Orlhac Fanny , Koole Michel , Malhaire Caroline
Published: September 2022

Objectives

To develop a visual ensemble selection of deep convolutional neural networks (CNN) for 3D segmentation of breast tumors using T1-weighted dynamic contrast-enhanced (T1-DCE) MRI.

Methods

Multi-center 3D T1-DCE MRI (n = 141) were acquired for a cohort of patients diagnosed with locally advanced or aggressive breast cancer. Tumor lesions of 111 scans were equally divided between two radiologists and segmented for training. The additional 30 scans were segmented independently by both radiologists for testing. Three 3D U-Net models were trained using either post-contrast images or a combination of post-contrast and subtraction images fused at either the image or the feature level. Segmentation accuracy was evaluated quantitatively using the Dice similarity coefficient (DSC) and the Hausdorff distance (HD95) and scored qualitatively by a radiologist as excellent, useful, helpful, or unacceptable. Based on this score, a visual ensemble approach selecting the best segmentation among these three models was proposed.

Results

The mean and standard deviation of DSC and HD95 between the two radiologists were equal to 77.8 ± 10.0% and 5.2 ± 5.9 mm. Using the visual ensemble selection, a DSC and HD95 equal to 78.1 ± 16.2% and 14.1 ± 40.8 mm was reached. The qualitative assessment was excellent (resp. excellent or useful) in 50% (resp. 77%).

Conclusion

Using subtraction images in addition to post-contrast images provided complementary information for 3D segmentation of breast lesions by CNN. A visual ensemble selection allowing the radiologist to select the most optimal segmentation obtained by the three 3D U-Net models achieved comparable results to inter-radiologist agreement, yielding 77% segmented volumes considered excellent or useful.

Key Points

• Deep convolutional neural networks were developed using T1-weighted post-contrast and subtraction MRI to perform automated 3D segmentation of breast tumors.

• A visual ensemble selection allowing the radiologist to choose the best segmentation among the three 3D U-Net models outperformed each of the three models.

• The visual ensemble selection provided clinically useful segmentations in 77% of cases, potentially allowing for a valuable reduction of the manual 3D segmentation workload for the radiologist and greatly facilitating quantitative studies on non-invasive biomarker in breast MRI.
Influence of preoperative weight loss on gastric wall thickness—analysis of laparoscopic sleeve gastrectomy histological material
Authors: Barski Krzysztof , Binda Artur , Jaworski Paweł , Gonciarska Agnieszka , Kudlicka Emilia , Żurkowska Joanna , Wawiernia Karolina , Tałałaj Marek , Wąsowski Michał , Tarnowski Wiesław
Published: September 2022

Purpose

The variables possibly enabling the prediction of gastric wall thickness during laparoscopic sleeve gastrectomy remain undetermined. The aim of the study was to identify preoperative factors affecting gastric wall thickness in patients undergoing laparoscopic sleeve gastrectomy.

Methods

The measurements of the double-wall thickness of gastric specimen excised during sleeve gastrectomy were taken at three locations after 15 s of compression with an applied pressure of 8 g/mm2. Statistical calculations were used to determine the influence of preoperative weight loss and other perioperative parameters on gastric wall thickness.

Results

The study involved one hundred patients (78 female; 22 male). The thickest tissue was observed at the antrum with the mean value 2.55 mm (range 1.77–4.0 mm), followed by the midbody, mean 2.13 mm (range 1.34–3.20 mm), and the fundus, mean 1.69 mm (range 0.99–2.69 mm). Positive relationships were found between gastric wall thickness and both preoperative weight loss and age in all three measured locations; p < 0.05. In a linear regression model, age and preoperative weight loss were found to be statistically significant and positive predictors of higher gastric wall thickness only at the antrum. Male patients were observed to have thicker gastric wall at all three locations as compared to female patients.

Conclusion

Preoperative weight loss should be considered an important factor influencing gastric wall thickness. Age and gender can also be helpful in predicting the varying tissue thickness. Anatomical region is a key factor determining thickness of the stomach walls.
Does the composition of urinary extracellular vesicles reflect the abundance of renal Na+/phosphate transporters?
Authors: Radvanyi Zsuzsi , Daryadel Arezoo , Pastor-Arroyo Eva Maria , Hernando Nati , Wagner Carsten Alexander
Published: September 2022

Studies addressing homeostasis of inorganic phosphate (Pi) are mostly restricted to murine models. Data provided by genetically modified mice suggest that renal Pi reabsorption is primarily mediated by the Na+/Pi cotransporter NaPi-IIa/Slc34a1, whereas the contribution of NaPi-IIc/Slc34a3 in adult animals seems negligible. However, mutations in both cotransporters associate with hypophosphatemic syndromes in humans, suggesting major inter-species heterogeneity. Urinary extracellular vesicles (UEV) have been proposed as an alternative source to analyse the intrinsic expression of renal proteins in vivo. Here, we analyse in rats whether the protein abundance of renal Pi transporters in UEV correlates with their renal content. For that, we compared the abundance of NaPi-IIa and NaPi-IIc in paired samples from kidneys and UEV from rats fed acutely and chronically on diets with low or high Pi. In renal brush border membranes (BBM) NaPi-IIa was detected as two fragments corresponding to the full-length protein and to a proteolytic product, whereas NaPi-IIc migrated as a single full-length band. The expression of NaPi-IIa (both fragments) in BBM adapted to acute as well to chronic changes of dietary Pi, whereas adaptation of NaPi-IIc was only detected in response to chronic administration. Both transporters were detected in UEV as well. UEV reflected the renal adaptation of the NaPi-IIa proteolytic fragment (but not the full-length protein) upon chronic but not acute dietary changes, while also reproducing the chronic regulation of NaPi-IIc. Thus, the composition of UEV reflects only partially changes in the expression of NaPi-IIa and NaPi-IIc at the BBM triggered by dietary Pi.
Identification of a new prognostic score for patients with high-grade metastatic GEP-NEN treated with palliative chemotherapy
Authors: Rosery Vivian , Mika Stephan , Schmid Kurt Werner , Reis Henning , Stuschke Martin , Treckmann Jürgen , Markus Peter , Schumacher Brigitte , Albers David , Mende Bastian , Lahner Harald , Wiesweg Marcel , Schuler Martin , Siveke Jens T. , Kasper Stefan
Published: September 2022

Purpose

High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN G3) are rare and heterogeneous malignancies with poor prognosis. Aim of this study was to develop prognosticators identifying those patients that derive the most benefit from currently available systemic therapies.

Methods

This retrospective analysis included 78 patients with metastatic GEP-NEN G3. For patients with imaging data available (n = 52), the overall response rate (ORR) and disease control rate (DCR) were evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). A Cox proportional hazard model was used to analyze the prognostic value of selected clinical and blood-based biomarkers. The impact of palliative chemotherapy regimens on time-to-treatment-failure (TTF) and overall survival (OS) was assessed.

Results

Median OS of the study cohort was 9.0 months (95% CI 7.0–11.1). The majority of patients received first-line treatment with platinum plus etoposide (83.3%). The ORR and DCR of the RECIST-evaluable subgroup were 34.6% and 76.9%. Median TTF upon first-line treatment was 4.9 months (95% CI 3.4–6.4). Multivariate analysis identified the Eastern Cooperative Oncology Group performance status (ECOG PS), lactate dehydrogenase (LDH) and absolute lymphocyte count as independent prognostic factors. A prognostic score based on these parameters discriminated patients with favorable and unfavorable outcomes.

Conclusion

Outcomes of patients with GEP-NEN G3 are still limited. A new prognostic score identifying those patients benefitting from current platinum/etoposide-based chemotherapy protocols may help as stratification factor in future trial design.
Cost-effectiveness analysis of NEPA, a fixed-dose combination of netupitant and palonosetron, for the prevention of highly emetogenic chemotherapy-induced nausea and vomiting: an international perspective
Authors: Nilsson Jonas , Piovesana Vittoria , Turini Marco , Lezzi Claudio , Eriksson Jennifer , Aapro Matti
Published: September 2022

Purpose

The aim of this study was to assess the cost-effectiveness of NEPA, a fixed-dose combination of oral netupitant (300 mg) and palonosetron (0.5 mg), compared to available treatments in Spain after aprepitant generic introduction in the market, and to discuss results in previously performed analyses in different wordwide settings.

Methods

A Markov model including three health states, complete protection, complete response at best and incomplete response, was used to evaluate the cost-effectiveness of NEPA versus common treatment options in Spain during 5 days after chemotherapy. Incremental costs including treatment costs and treatment failure management cost as well as incremental effects including quality adjusted life days (QALDs) and emesis-free days were compared between NEPA and the comparator arms. The primary outcomes were cost per avoided emetic event and cost per QALDs gained.

Results

NEPA was dominant (more effective and less costly) against aprepitant combined with palonosetron, and fosaprepitant combined with granisetron, while, compared to generic aprepitant plus ondansetron, NEPA showed an incremental cost per avoided emetic event of €33 and cost per QALD gained of €125.

Conclusion

By most evaluations, NEPA is a dominant or cost-effective treatment alternative to current antiemetic standards of care in Spain during the first 5 days of chemotherapy treatment in cancer patients, despite the introduction of generics. These results are in line with previously reported analyses throughout different international settings.